Alison graduated with Bsc (Hons) and then PhD in Organic Synthesis from University of New South Wales. Following her PhD, in 1994 she joined the Johnson and Johnson Research Pty. Ltd as a Research Fellow, working on projects in the areas of drug discovery and medicinal chemistry.
Then for 5 years (2003-2008) she held a Research Manager position in the Johnson & Johnson Research Pharmaceutical Research Laboratory (JJRPRL) housed in School of Chemistry, University of Wollongong (UOW).
Can supervise: YES
- Design and synthesis of FtsZ inhibitors as potential antibacterial agents
- Drug discovery (design and synthesis of bioactive molecules)
- Natural products for drug discovery: focusing on using natural products, as chemical scaffolds for drug discovery.
- Design and synthesis of alkaloid-like compounds for drug discovery, using the Bridging Ritter reactions
- Computer-aid molecular modelling for drug discovery
- Organic Chemstry
- Medicinal Chemistry
- Spectroscopy and Structures
- Strategy in Synthesis
Prasansuklab, A, Theerasri, A, Payne, M, Ung, AT & Tencomnao, T 2018, 'Acid-base fractions separated from Streblus asper leaf ethanolic extract exhibited antibacterial, antioxidant, anti-acetylcholinesterase, and neuroprotective activities.', BMC complementary and alternative medicine, vol. 18, no. 1, pp. 223-223.View/Download from: UTS OPUS or Publisher's site
Streblus asper is a well-known plant native to Southeast Asia. Different parts of the plant have been traditionally used for various medicinal purposes. However, there is very little scientific evidence reporting its therapeutic benefits for potential treatment of Alzheimer's disease (AD). The study aimed to evaluate antibacterial, antioxidant, acetylcholinesterase (AChE) inhibition, and neuroprotective properties of S. asper leaf extracts with the primary objective of enhancing therapeutic applications and facilitating activity-guided isolation of the active chemical constituents.The leaves of S. asper were extracted in ethanol and subsequently fractionated into neutral, acid and base fractions. The phytochemical constituents of each fraction were analyzed using GC-MS. The antibacterial activity was evaluated using a broth microdilution method. The antioxidant activity was determined using DPPH and ABTS radical scavenging assays. The neuroprotective activity against glutamate-induced toxicity was tested on hippocampal neuronal HT22 cell line by evaluating the cell viability using MTT assay. The AChE inhibitory activity was screened by thin-layer chromatography (TLC) bioautographic method.The partition of the S. asper ethanolic leaf extract yielded the highest mass of phytochemical constitutions in the neutral fraction and the lowest in the basic fraction. Amongst the three fractions, the acidic fraction showed the strongest antibacterial activity against gram-positive bacteria. The antioxidant activities of three fractions were found in the order of acidic > basic > neutral, whereas the decreasing order of neuroprotective activity was neutral > basic > acidic. TLC bioautography revealed one component in the neutral fraction exhibited anti-AChE activity. While in the acid fraction, two components showed inhibitory activity against AChE. GC-MS analysis of three fractions showed the presence of major phytochemical constituents including terpenoids, steroids, phenol...
Sun, Y, Zhang, W, Wang, B, Xu, X, Chou, J, Shimoni, O, Ung, AT & Jin, D 2018, 'A supramolecular self-assembly strategy for upconversion nanoparticle bioconjugation.', Chemical communications (Cambridge, England), vol. 54, no. 31, pp. 3851-3854.View/Download from: UTS OPUS or Publisher's site
An efficient surface modification for upconversion nanoparticles (UCNPs) is reported via supramolecular host-guest self-assembly. Cucurbituril (CB) can provide a hydrophilic surface and cavities for most biomolecules. High biological efficiency, activity and versatility of the approach enable UCNPs to be significantly applied in bio-imaging, early disease detection, and bio-sensing.
Williams, SG, Bhadbhade, M, Bishop, R & Ung, AT 2017, 'An alkaloid-like 3-azabicyclo[3.3.1]non-3-ene library obtained from the bridged Ritter reaction', Tetrahedron, pp. 116-128.View/Download from: UTS OPUS or Publisher's site
Gao, J, Djaidi, D, Marjo, CE, Bhadbhade, MM, Ung, AT & Bishop, R 2017, 'Weak Intermolecular Forces, but High Melting Points', Australian Journal of Chemistry, vol. 70, no. 5, pp. 538-545.View/Download from: UTS OPUS or Publisher's site
© 2017 CSIRO. The poorly soluble racemic compound 6,6a,13,13a-tetrahydropentaleno[1,2-b:4,5-b]diquinoline (4) has an exceptionally high melting point range of 352-354°C despite its low molar mass (308.38) and a structure containing only 40 atoms (38 of which are C and H). Analysis of the X-ray crystal structure and Hirshfeld surface of 4, along with comparison with its isostructural homologue 2, reveals how this occurs in the absence of Pauling-type hydrogen bonding. Excellent complementarity between homochiral molecules of 4 allows formation of enantiomerically pure layers using C-H, aromatic , and C-HN interactions. The alternating layers of opposite handedness are then crosslinked by means of aza-1,3-peri hydrogen interactions. This bifurcated C-HNH-C motif acts as a molecular clip creating a highly rigid network structure. The role of weaker intermolecular forces in influencing the solubility and bioavailability of potential drug molecules is discussed in the context of the popular Lipinski 'rule of 5' guidelines.
Williams, SG, Bhadbhade, M, Bishop, R & Ung, AT 2017, 'Synthesis and Crystal Structure of Unexpected (1S,4R,5R,6S)-4-Cyano-2,2,6-trimethyl-3-azabicyclo[3.3.1]nonan-6-yl Acetate', Australian Journal of Chemistry, vol. 70, pp. 1269-1273.View/Download from: UTS OPUS or Publisher's site
The reaction of (–)-b-pinene with KCN under a mild bridged Ritter reaction gave (1S,5R,6S)-2,2,6-trimethyl-3-aza-bicyclo
[3.3.1]non-3-en-6-yl acetate that subsequently reacted to provide an unexpected (1S,4R,5R,6S)-4-cyano-2,2,6-trimethyl-3-
azabicyclo[3.3.1]nonane-6-yl acetate. The structure of the compound was determined by high-resolution mass spectrometry,
and IR and NMR spectroscopy and confirmed by single crystal X-ray crystallography. The compound crystallises in the
monoclinic P21 space group, with unit cell parameters a 8.6120 (17), b 7.4570 (15), c 11.189 (2) A , and b 110.16 (3)8.
Pascali, G, Matesic, L, Zhang, B, King, A, Robinson, AJ, Ung, AT & Fraser, BH 2017, 'Sulfur - fluorine bond in PET radiochemistry', EJNMMI Radiopharmacy and Chemistry, vol. 2, no. 9, pp. 2-18.View/Download from: UTS OPUS or Publisher's site
The importance of the sulfur-fluorine bond is starting to increase in modern medicinal chemistry literature. This is due to a better understanding of the stability and reactivity of this moiety depending on the various oxidation states of sulfur. Furthermore, several commercial reagents used for mild and selective fluorination of organic molecules are based on the known reactivity of S-F groups. In this review, we will show how these examples are translating into the 18F field, both for use as stable tags in finished radiopharmaceuticals and as mildly reactive fluoride-relay intermediates. Finally, we also discuss current opportunities where examples of non-radioactive S-F applications/chemistry may be translated into future 18F radiochemistry applications.
Roseblade, A, Ung, A & Bebawy, M 2017, 'Synthesis and in vitro biological evaluation of thiosulfinate derivatives for the treatment of human multidrug-resistant breast cancer.', Acta Pharmacologica Sinica, vol. 38, no. 10, pp. 1353-1368.View/Download from: UTS OPUS or Publisher's site
Organosulfur compounds derived from Allium vegetables have long been recognized for various therapeutic effects, including anticancer activity. Allicin, one of the main biologically active components of garlic, shows promise as an anticancer agent; however, instability makes it unsuitable for clinical application. The aim of this study was to investigate the effect of stabilized allicin derivatives on human breast cancer cells in vitro. In this study, a total of 22 stabilized thiosulfinate derivatives were synthesized and screened for their in vitro antiproliferative activities against drug-sensitive (MCF-7) and multidrug-resistant (MCF-7/Dx) human adenocarcinoma breast cancer cells. Assays for cell death, apoptosis, cell cycle progression and mitochondrial bioenergetic function were performed. Seven compounds (4b, 7b, 8b, 13b, 14b, 15b and 18b) showed greater antiproliferative activity against MCF-7/Dx cells than allicin. These compounds were also selective towards multidrug-resistant (MDR) cells, a consequence attributed to collateral sensitivity. Among them, 13b exhibited the greatest anticancer activity in both MCF-7/Dx and MCF-7 cells, with IC50 values of 18.54±0.24 and 46.50±1.98 mol/L, respectively. 13b altered cellular morphology and arrested the cell cycle at the G2/M phase. Additionally, 13b dose-dependently induced apoptosis, and inhibited cellular mitochondrial respiration in cells at rest and under stress. MDR presents a significant obstacle to the successful treatment of cancer clinically. These results demonstrate that thiosulfinate derivatives have potential as novel anticancer agents and may offer new therapeutic strategies for the treatment of chemoresistant cancers.
Pyne, S.G., Jatisatienr, A., Mungkornasawakul, P., Ung, A.T., Limtrakul, P., Sastraruji, T., Sastraruji, K., Chaiyong, S., Umsumarng, S., Baird, M., Dau, X.D. & Ramli, R.A. 2017, 'Phytochemical, Synthetic and Biological Studies on Stemona andStichoneuron Plants and Alkaloids: A Personal Perspective', Natural Product Communications, vol. 12, no. 8, pp. 1365-1369.
Ung, AT, West, AN, Phillips, MJA & Williams, SG 2016, 'Synthesis of alkaloid-like compounds via the bridging Ritter reactions II', Monatshefte für Chemie - Chemical Monthly, vol. 147, pp. 1737-1746.View/Download from: UTS OPUS or Publisher's site
The bridging Ritter reactions are considered to be efficient synthetic methods rapidly providing access to alkaloid-like compounds in a few steps from inexpensive starting materials. In this manuscript, we report the synthesis of benzo[c]azepine derivatives bearing either amide or hydroxyl groups via the bridging Ritter reactions. These compounds are diastereoisomers of a known AChE inhibitor. All the structures were fully characterised by NMR spectroscopy and high-resolution mass spectrometry. NMR spectral analysis of diastereoisomers has allowed for the relative stereochemistry of the AChE inhibitor to be established.
Palee, J, Dheeranupattana, S, Wangkarn, S, Pyne, SG & Ung, AT 2016, 'Effects of chitosan and salicylic acid on stemona alkaloid production in hydroponic culture of stemona curtisii Hook. f.', Chiang Mai Journal of Science, vol. 43, no. 5, pp. 1070-1076.View/Download from: UTS OPUS
© 2016, Chiang Mai University. All rights reserved. The objective of this study was to investigate the effects of the elicitors, salicylic acid (SA) and chitosan, on the improvement of Stemona alkaloid production in hydroponic cultures of S. curtisii. In vitro plantlets were used as plant materials. The elicitors were added into the culture medium and samples of the roots and medium were collected on week 2 and 4 after the elicitor addition and then analyzed for Stemona alkaloid production by high performance liquid chromatography (HPLC). This study revealed that both SA and chitosan increased production of three Stemona alkaloids and that chitosan is better than SA for the enhancement of the production of these alkaloids. The elicitation by 20 mg L-1of chitosan for 4 weeks induced highest amount of oxyprotostemonine (274.31 g g-1DW) stemocurtisine (35.46 g g-1DW) and stemocurtisinol (99.48g g-1DW), which were 1.9, 2.0 and 1.5 fold higher than that of the control, respectively.
Perkins, G, Khatib, O, Peterson, M, Kallinen, A, Pham, T, Ung, AT, Greguric, I & Pascali, G 2016, 'Microfluidic implementation of Ru-catalyzed methylation of amines using CO2 as carbon source', Journal of Flow Chemistry, vol. 6, no. 4, pp. 302-308.View/Download from: UTS OPUS or Publisher's site
Carbon dioxide chemistry is an area of continuing growth in recent times, due to socioeconomic and environmental reasons. Several methods have now been reported for obtaining N-methylation on primary and secondary amines directly from CO2. We have translated in two microfluidic setups (Slug Flow [SF] and Tube-in-Tube [TiT]) a ruthenium (Ru)-catalyzed process previously reported using a pressure vessel. Here, we demonstrate how the SF approach is more efficient but requires more input to reach a steady state, while the TiT system is less efficient but more tuneable.We have tested these processes on three model amines and two radiopharmaceutical precursors that are routinely used in 11C chemistry. The microfluidic processes tested are also potentially more efficient than the pressure vessel counterpart, in terms of amount of Ru catalyst needed (1% vs. 10%) and projected reaction completion time.
Umsumarng, S, Pitchakarn, P, Sastraruji, K, Yodkeeree, S, Ung, AT, Pyne, SG & Limtrakul, P 2015, 'Reversal of human multi-drug resistance leukaemic cells by stemofoline derivatives via inhibition of P-glycoprotein function.', Basic & clinical pharmacology & toxicology, vol. 116, no. 5, pp. 390-397.View/Download from: Publisher's site
Our previous study reported multi-drug resistance (MDR) reversing properties of synthetic stemofoline derivatives (STFD), OH-A1, NH-B6 and NH-D6 on P-glycoprotein (P-gp) overexpressing leukaemic cells (K562/Adr); however, the mechanism was unclear. In this study, we further investigated whether the STFD reverse MDR through either the inhibition of P-gp function or expression in K562/Adr cells, or both. The P-gp functional studies showed that the STFD increased the accumulation of calcein-AM, rhodamine 123 and [(14) C]-doxorubicin in K562/Adr cells, while the effects have not been seen in their parental sensitive cancer cell line (K562). Further, the STFD did not alter the P-gp expression as determined by Western blotting. This study concludes that the STFD reverse MDR via the inhibition of P-gp function. The efficacy of the STFD to inhibit P-gp function followed the order: NH-B6 > OH-A1 > NH-D6. These compounds could be introduced as candidate molecules for treating cancers exhibiting P-gp-mediated MDR.
Mondal, AK, Su, D, Chen, S, Ung, A, Kim, HS & Wang, G 2015, 'Mesoporous MnCo2O4 with a flake-like structure as advanced electrode materials for lithium-ion batteries and supercapacitors.', Chemistry (Weinheim an der Bergstrasse, Germany), vol. 21, no. 4, pp. 1526-1532.View/Download from: Publisher's site
A mesoporous flake-like manganese-cobalt composite oxide (MnCo2O4) is synthesized successfully through the hydrothermal method. The crystalline phase and morphology of the materials are characterized by X-ray diffraction, field-emission scanning electron microscopy, transmission electron microscopy, and Brunauer-Emmett-Teller methods. The flake-like MnCo2O4 is evaluated as the anode material for lithium-ion batteries. Owing to its mesoporous nature, it exhibits a high reversible capacity of 1066mAhg(-1), good rate capability, and superior cycling stability. As an electrode material for supercapacitors, the flake-like MnCo2O4 also demonstrates a high supercapacitance of 1487Fg(-1) at a current density of 1Ag(-1), and an exceptional cycling performance over 2000 charge/discharge cycles.
Roseblade, A, Luk, F, Ung, A & Bebawy, M 2015, 'Targeting microparticle biogenesis: a novel approach to the circumvention of cancer multidrug resistance.', Current Cancer Drug Targets, vol. 15, no. 3, pp. 205-214.View/Download from: UTS OPUS or Publisher's site
Microparticles (MPs) are released from most eukaryotic cells after the vesiculation of the plasma membrane and serve as vectors of long and short-range signaling. MPs derived from multidrug resistant (MDR) cancer cells carry molecular components of the donor cell such as nucleic acids and proteins, and can alter the activity of drug-sensitive recipient cells through the transfer of their cargo. Given the substantial role of MPs in the acquisition and dissemination of MDR, we propose that the inhibition of MP release provides a novel therapeutic approach. This study characterises the effect of a panel of molecules known to act on MP-biosynthetic pathways. We demonstrate a differential effect by these molecules on MP inhibition that appear dependent on the release of intracellular calcium stores following activation with the calcium ionophore A23187. Calpain inhibitor, PD-150606; a selective inhibitor of Rho-associated, coiled-coil containing protein kinase (ROCK), Y-27632; and the vitamin B5 derivative pantethine, inhibited MP release only upon prior activation with A23187. Calpain inhibitor II showed significant inhibition in the absence of cell activation, whereas the vitamin B5 derivatives cystamine dihydrochloride and cysteamine hydrochloride showed no effect on MP inhibition under either condition. In contrast the classical pharmacological inhibitor of MDR, the calcium channel blocker Verapamil, showed an increase in MP formation on resting cells. These results suggest a potential role for calcium in the mechanism of action for PD-150606, Y-27632 and pantethine. These molecules, together with calpain inhibitor II have shown promise as modulators of MP release and warrant consideration as potential candidates for the development of an alternative therapeutic strategy for the prevention of MP-mediated MDR in cancer.
Ung, AT, Williams, SG, Angeloski, A, Ashmore, J, Kuzhiumparambil, U, Bhadbhade, M & Bishop, R 2014, 'Formation of 3-azabicyclo[3.3.1]non-3-enes: imino amides vs. imino alkenes', Monatshefte fur Chemie, vol. 145, no. 6, pp. 983-992.View/Download from: UTS OPUS or Publisher's site
An effective method for synthesising alkaloidlike compounds containing the 3-azabicyclo[3.3.1]non-3-ene core structure was successfully carried out in a stereoselective manner via the bridged-Ritter reactions. Important optically active 6-alkyl(aryl)amido-4-alkyl( aryl)-2,2,6-trimethyl-3-azabicyclo[3.3.1]non-3-enes (imino amides) and 4-alkyl(aryl)-2,2,6-trimethyl-3-azabicyclo[3.3.1]nona-3,6-dienes (imino alkenes) were obtained in one step from (-)-b-pinene and the respective nitriles in the presence of concentrated H2SO4. The relative compositions of these products were controlled by varying the reaction conditions. Kinetic studies were conducted to enable a mechanistic understanding of the reaction pathways.
Mondal, AK, Su, D, Chen, S, Zhang, J, Ung, A & Wang, G 2014, 'Microwave-assisted synthesis of spherical -Ni(OH)2superstructures for electrochemical capacitors with excellent cycling stability', Chemical Physics Letters, vol. 610-611, pp. 115-120.View/Download from: UTS OPUS or Publisher's site
A novel single-step microwave-assisted process has been developed to synthesize spherical -Ni(OH)2superstructures without using any templates. Structure characterizations show that the spherical -Ni(OH)2composed of twisted nanosheets was obtained. The electrochemical properties of the as-prepared materials were evaluated by cyclic voltammetry and chronopotentiometry technology in 2 M KOH solution. Due to the unique morphology, the prepared -Ni(OH)2electrode displays a high specific capacitance of 2147 F g-1at a discharge current of 1 A g-1and outstanding cycling stability (99.5% capacitance retained after 2000 cycles), suggesting its potential application as an efficient electrode material for high-performance electrochemical capacitors. © 2014 Elsevier B.V.
Luong, S, Ung, AT, Kalman, J & Fu, S 2014, 'Transformation of codeine and codeine-6-glucuronide to opioid analogues by urine adulteration with pyridinium chlorochromate: potential issue for urine drug testing', RAPID COMMUNICATIONS IN MASS SPECTROMETRY, vol. 28, no. 14, pp. 1609-1620.View/Download from: Publisher's site
Umsumarng, S, Pintha, K, Pitchakarn, P, Sastraruji, K, Sastraruji, T, Ung, AT, Jatisatienr, A, Pyne, SG & Limtrakul, P 2013, 'Inhibition of P-Glycoprotein Mediated Multidrug Resistance by Stemofoline Derivatives', Chemical and Pharmaceutical Bulletin, vol. 61, no. 4, pp. 399-404.View/Download from: UTS OPUS or Publisher's site
Resistance to chemotherapy in cancer patients has been correlated to the overexpression of the ATP-binding cassette (ABC) drug transporters including P-glycoprotein (P-gp) that actively efflux chemotherapeutic drugs from cancer cells. We examined the mutidrug resistance reversing property of stemofoline derivatives in drug-resistance human cervical carcinoma (KB-V1) and human leukemic (K562/Adr) cell lines that overexpress P-gp. Didehydrostemofoline and eleven of its derivatives were synthesized and the cytotoxicity and their effect on doxorubicin, vinblastine and paclitaxel sensitivity in drug resistant (KB-V1 and K562/Adr) and drug sensitive (KB-3-1 and K562) cell lines by a 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay were determined. We found that three out of the twelve stemofoline derivatives including OH-A1, NH-B6 and NH-D6 showed commitment efficiency to increase sensitivity to doxorubicin, vinblastine and paclitaxel in KB-V1 cells and increase sensitivity to doxorubicin, and paclitaxel in K562/Adr cells whereas the effects have not been seen in their parental sensitive cancer cell lines (KB-3-1 and K562). These results indicate that stemofoline derivatives reversed P-gp-mediated multidrug resistance in vitro, and thus could be developed as effective. chemosensitizers to treat multidrug-resistant cancers. The molecular mechanism of modulation of P-gp would be further determined.
Roseblade, AP, Luk, F, Rawling, T, Ung, AT, Grau, G & Bebawy, M 2013, 'Cell-Derived Microparticles: New Targets in the Therapeutic management of disease', Journal of Pharmacy & Pharmaceutical Sciences, vol. 16, no. 2, pp. 238-253.View/Download from: UTS OPUS or Publisher's site
Intercellular communication is essential to maintain vital physiological activities and to regulate the organisms phenotype. There are a number of ways in which cells communicate with one another. This can occur via autocrine signaling, endocrine signaling or by the transfer of molecular mediators across gap junctions. More recently communication via microvesicular shedding has gained important recognition as a significant pathway by which cells can coordinate the spread and dominance of selective traits within a population. Through this communication apparatus, cells can now acquire and secure a survival advantage, particularly in the context of malignant disease. This review aims to highlight some of the functions and implications of microparticles in physiology of various disease states, and present a novel therapeutic strategy through the regulation of microparticle production.
Ung, AT, Pyne, S, Bischoff, F, Lesage, AS, Skelton, B & White, AH 2013, 'Synthesis and inhibitory activities at mGluRs of 3-alkylated and N-alkylated cyclopentyl-glutamate analogues', Tetrahedron, vol. 69, no. 12, pp. 2577-2587.View/Download from: UTS OPUS or Publisher's site
The conformationally restricted glutamate analogues, 3-alkyl-1-amino-2-cyclopentene-1,3-dicarboxylates and N-alkylated analogues have been prepared in a regioselective and diastereoselective manner. From the biological studies of the 3-alkylated analogue
Wang, Y, Su, D, Ung, AT, Ahn, J & Wang, G 2012, 'Hollow CoFe(2)O(4) nanospheres as a high capacity anode material for lithium ion batteries', Nanotechnology, vol. 23, no. 5, pp. 1-6.View/Download from: UTS OPUS or Publisher's site
Hollow structured CoFe(2)O(4) nanospheres were synthesized by a hydrothermal method. The uniform hollow nanosphere architecture of the as-prepared CoFe(2)O(4) has been confirmed by field emission scanning electron microscopy and transmission electron microscopy analysis, which give an outer diameter of 200-300 nm and a wall thickness of about 100 nm. CoFe(2)O(4) nanospheres exhibited a high reversible capacity of 1266 mA h g(-1) with an excellent capacity retention of 93.6% over 50 cycles and an improved rate capability. CoFe(2)O(4) could be a promising high capacity anode material for lithium ion batteries.
Hemtasin, C, Ung, AT, Kanokmedhakul, S, Kanokmedhakul, K, Bishop, R, Sastraruji, T & Bishop, D 2012, 'Synthesis of alkaloid-like compounds via the bridging Ritter Reaction', Monatshefte fÃ¼r Chemie, vol. 143, no. 6, pp. 955-963.View/Download from: UTS OPUS or Publisher's site
Alkaloid-like compounds containing a benzo[c]azepine core structure were successfully prepared in three steps from H-dibenzo[a,d]cyclohepten-5-ol via the bridging Ritter reaction. Biological studies of these compounds revealed that some of them are AChE inhibitors and antimalarial agents.
Sastraruji, T, Pyne, SG & Ung, AT 2012, 'Oxidation of acyclic alkenes and allyl and benzyl ethers with DIB/t-BuOOH/Mg(OAc)2', Tetrahedron, vol. 68, no. 2, pp. 598-602.View/Download from: UTS OPUS or Publisher's site
Oxidation of (11Z)-1',2'-didehydrostemofoline with DIB/TBHP/Mg(OAc)(2)center dot 4H(2)O resulted in oxidative cleavage of the C-11-C-12 double bond instead of the desired allylic oxidation of the 1-butenyl side chain. Stemofoline gave a similar result. The oxidation of more simple terminal alkenes was regioselective and gave vinyl ketones while allyl and benzyl ethers gave acrylate and benzoate esters, respectively. Allyl and benzyl ethers could be chemoselectively oxidized in the presence of a terminal alkene or benzyl group. Oxidation of an internal alkene was poorly regioselective, in contrast to the oxidation of 1-substituted cyclohexenes.
Sastraruji, K, Sastraruji, T, Ung, AT, Griffith, R, Jatisatienr, A & Pyne, SG 2012, 'Synthesis of stemofoline analogues as acetylcholinesterase inhibitors', Tetrahedron, vol. 68, no. 35, pp. 7103-7115.View/Download from: UTS OPUS or Publisher's site
Thirty-two new stemofoline analogues were prepared from didehydrostemofoline for studies as AChE inhibitors. C-3 Side-chain modified amino, carbamate, triazole and oxazole stemofoline derivatives were prepared. In general the amine derivatives were found to be stronger inhibitors of AChE than their alcohol analogues that we previously reported. Compounds 5 and 26, with small C-3 side-chain substituents, were two of the most active inhibitors. Preliminary molecular docking studies suggested that these compounds may inhibit AChE by binding horizontally along the passage of the active-site gorge and block access to acetylcholine.
Palee, J, Dheeranupattana, S, Jatisatienr, A, Wangkarn, S, Mungkornasawakul, P, Pyne, SG, Ung, AT & Sastraruji, T 2012, 'Influence of Plantlet Age and Different Soilless Culture on Acclimatization of Stemona curtisii Hook.f.', Asian Journal of Plant Sciences, vol. 11, no. 6, pp. 294-299.View/Download from: UTS OPUS or Publisher's site
The aim of this experiment was to study the optimal age of Stemona curtisii plantlets for acclimatization. The in vitro shoots of S. curtisii were cultured on Murashige and Skoog solid medium supplemented with 1 mg L-1 naphthalene acetic acid to induce roots. Then, the plantlets from in vitro culture of 4, 8 and 12 week-old were transferred into the soil and their survival rate during the acclimatization process in the greenhouse was investigated. It was found that the 8 week-old plantlets had the highest survival rate of 80%. However, to enhance the survival rate of these plantlets, a soilless culture technique as a possible approach for the acclimatization was considered. Eight week-old plantlets were transferred into either, soil, a hydroponic system (nutrient film technique), coconut fiber or sand. The plantlets which were cultivated in coconut fiber or hydroponic culture showed 100% survival rate with the highest average number of new roots per plant. However, the mean root length of the plantlets grown in hydroponic system was significantly higher than that grown in coconut fiber.
Chotikadachanarong, K., Dheeranupattana, S., Jatisatienr, A., Wangkarn, S., Mungkornasawakul, P., Pyne, S.G., Ung, A.T. & Sastraruji, T. 2011, 'Influence of salicylic acid on alkaloid production by root cultures of Stemona curtisii Hook. F.', Current Research Journal of Biological Sciences, vol. 3, no. 4, pp. 322-325.
To enhance the production of oxyprotostemonine, stemocurtisine and stemocurtisinol (the important insecticidal alkaloids) by root cultures of Stemona curtisii Hook. F. (Thai vernacular, Non Tai Yak, Family Stemonaceae). The roots were cultured on semi-solid MS medium contg. 1 mg/L NAA with different concns. of salicylic acid for 16 wk. The quantity of the individual alkaloids was detd. by HPLC. The highest prodn. of oxyprotostemonine (7.192 mg/g dw), stemocurtisine (0.039 mg/g dw) and stemocurtisinol (0.197 mg/g dw) occurred when the roots were stimulated by 500 mg/L salicylic acid.
Ung, AT, Pyne, SG, Joeffreys, G, Skelton, BW & White, AH 2011, 'Synthesis of 2-acetyl-5-(1,2,3,4,5,6-hexahydroxyhexyl) thiazoles', Monatshefte fÃ¼r Chemie - Chemical, vol. 142, no. 3, pp. 297-303.View/Download from: UTS OPUS or Publisher's site
The syntheses of two diastereoisomers of 2-acetyl-5-(1,2,3,4,5,6-hexahydroxyhexyl) thiazole are reported. The synthesis of these diastereoisomers involved the coupling of 5-metallated 2-(1,1-dimethoxyethyl)thiazole with a Weinreb amide derived from d-gluconolactone, followed by asymmetric reduction of the ketone thus prepared. The stereochemistries and structures of some key compounds were determined by single-crystal X-ray structural analysis.
Sastraruji, T, Chaiyong, S, Jatisatienr, A, Pyne, SG, Ung, AT & Lie, W 2011, 'Phytochemical Studies on Stemona aphylla: Isolation of a New Stemofoline Alkaloid and Six New Stemofurans', Journal of Natural Products, vol. 74, no. 1, pp. 60-64.View/Download from: UTS OPUS or Publisher's site
A new stemofoline alkaloid, (2'S)-hydroxy-(11S,12R)-dihydrostemofoline (3), new stemofurans M-R (8-13), and known compounds stemofoline (1), (2?S)-hydroxystemofoline (2), stemofuran E (4), stemofuran F (5), stemofuran J (6), and stilbostemin F (7) have been isolated from the root extracts of Stemona aphylla. The structures and relative configurations of these new compounds have been determined by spectroscopic data interpretation and from semisynthetic studies. These natural and semisynthetic alkaloids were tested for acetylcholinesterase inhibitory activities and were found to be 10-20 times less active than 1?,2?-didehydrostemofoline itself. Stemofurans 4, 6, 8, 11, and 13 were tested for their antibacterial and antifungal activities. Three of these showed antibacterial activities against MRSA with MIC values of 15.6 ?g/mL
Sastraruji, K, Sastraruji, T, Pyne, SG, Ung, AT, Jatisatienr, A & Lie, W 2010, 'Semi-Synthesis and Acetylcholinesterase Inhibitory Activity of Stemofoline Alkaloids and Analogs', Journal of Natural Products, vol. 73, no. 5, pp. 935-941.View/Download from: UTS OPUS or Publisher's site
Semisynthesis of the known Stemona alkaloids oxystemofoline (7) and methoxystemofoline (8) has been achieved starting from (11Z)-1â²,2â²-didehydrostemofoline (6), which confirmed their structures and absolute configurations. The synthesis of (1â²R)-...
Mbere-Nguyen, U, Ung, AT & Pyne, SG 2010, 'Synthesis of 2'-Aminoalkyl-1-benzylisoquinoline derivatives, medium sized ring analogues with mu opiod receptor binding activities', Tetrahedron, vol. 66, no. 23, pp. 4133-4143.View/Download from: UTS OPUS or Publisher's site
Novel 20-aminoalkyl-1-benzylisoquinoline compounds and medium size ring analogues have been prepared using reductive alkylation methods. Four of these analogues were tested for biological activity across 48 different CNS receptors and were showed to have binding activities at the mu opiod receptor.
Chaiyong, S, Jatisatienr, A, Mungkornasawakul, P, Sastraruji, T, Pyne, SG, Ung, AT, Urathamakul, T & Lie, W 2010, 'Phytochemical Investigations of Stemona curtisii and Synthetic Studies on Stemocurtisine', Journal of Natural Products, vol. 73, no. 11, pp. 1833-1838.View/Download from: UTS OPUS or Publisher's site
The isolation of two new Stemona alkaloids, 1-hydroxyprotostemonine and stemocurtisine N-oxide, and a new benzofuran, stemofuran L, from the root extracts of Stemona curtisii is reported. The major known alkaloids from this plant extract, stemocurtisine, stemocurtisinol, and oxyprotostemonine, were also isolated along with oxystemokerrine N-oxide. The nonalkaloid components of this extract included a new benzofuran derivative, stemofuran L, the known stemofurans F, J, and K, dihydro-Î³-tocopherol, and stigmasterol. Stemocurtisine and stemocurtisinol were converted to their respective N-oxides by oxidation. Stemocurtisine was converted to a tetracyclic derivative by oxidative cleavage of the Î³-butyrolactone ring, while stemocurtisinol gave a novel lactam derivative by oxidative cleavage of the C-4 side chain under basic conditions. The acetylcholinesterase inhibitory activities of some known and new alkaloids and their derivatives are also reported. All were 10-20 times less active as acetylcholinesterase inhibitors than the pyrrolo[1,2-a]azepine Stemona alkaloids stemofoline and 1â²,2â²-didehydrostemofoline. None of the stemofuran compounds showed significant antibacterial or antifungal activities.
Mungkornasawakul, P, Pyne, SG, Ung, AT, Jatisatienr, A & Willis, AC 2009, 'Stemofoline ethyl acetate solvate', ACTA CRYSTALLOGRAPHICA SECTION E-STRUCTURE REPORTS ONLINE, vol. 65, pp. O1878-U3157.View/Download from: UTS OPUS or Publisher's site
Batenburg-Nguyen, U, Ung, AT & Pyne, SG 2009, 'The synthesis of carbon linked bis-benzylisoquinolines using Mizoroki-Heck and Sonagashira coupling reactions', Tetrahedron, vol. 65, no. 1, pp. 318-327.View/Download from: UTS OPUS or Publisher's site
Novel laudanosine dimers in which two laudanosine units are linked at C-2? via a two or three-carbon linker (alkane, alkene or alkyne) have been prepared using palladium-catalysed cross-coupling reactions (MizorokiHeck and Sonagashira reactions). In one example, a second three-carbon linker between the two isoquinoline N-atoms was also present leading to a novel macrocyclic ring system.
Mungkornasawakul, P, Chaiyong, S, Sastraruji, T, Jatisatienr, A, Jatisatienr, C, Pyne, SG, Ung, AT, Korth, J & Lie, W 2009, 'Alkaloids from the Roots of Stemona aphylla', Journal of Natural Products, vol. 72, no. 5, pp. 848-851.View/Download from: UTS OPUS or Publisher's site
Three known compounds, stemofoline (1), (2'S)-hydroxystemofoline (2), and (11Z)-1',2'-didehydrostemofoline (3), along with two new alkaloids, stemaphylline (4) and stemaphylline-N-oxide (5), have been isolated from a root extract of Stemona aphylla. The structures of these alkaloids were determined on the basis of their spectroscopic data. The analysis of the crude dichloromethane extract by GC-MS in the EIMS mode showed the presence of alkaloids 1-4, the alkaloid 11, and stilbostemin R (12). The crude dichloromethane extract and 4 were tested for their comparative biological activities. The results of their acetylcholinesterase (AChE) inhibitory activities showed that the crude extract had higher activity than that of 4. The insecticidal properties of the crude extract and 4, using a topical application, showed that 4 had an activity similar to the positive control, methomyl, whereas the crude extract had much lower activity. Their antimicrobial activity against Escherichia coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas auruginosa ATCC 27853, and Candida albicans ATCC 90028 was weak (MIC 62.5-125 ?g/mL, MBC 125-250 ?g/mL, MFC 125 ?g/mL) but much higher than that of the crude extract.
Sastraruji, K, Pyne, SG, Ung, AT, Mungkornasawakul, P, Lie, W & Jatisatienr, A 2009, 'Structural Revision of Stemoburkilline from an E-Alkene to a Z-Alkene', Journal of Natural Products, vol. 72, no. 2, pp. 316-318.View/Download from: UTS OPUS or Publisher's site
Semisynthesis studies starting from (11Z)-1?,2?-didehydrostemofoline (4) indicated that the known Stemona alkaloid stemoburkilline is the Z-isomer and not the E-isomer as initially reported. The semisynthesis involved conversion of (11Z)-1?,2?-didehydrostemofoline (4) to 11(S),12(S)-dihydrostemofoline (3) followed by a stereoselective base-catalyzed ring-opening reaction to give (Z)-stemoburkilline (8). The same product was obtained using a similar synthetic protocol starting from isostemofoline (6) via a based-catalyzed ring-opening reaction of 11(S),12(R)-dihydrostemofoline (1). A re-examination of the crude root extracts of Stemona burkillii Prain and further NOE studies established stemoburkilline as the Z-isomer
Baird, MC, Pyne, SG, Ung, AT, Lie, W, Sastraruji, T, Jatisatienr, A, Jatisatienr, C, Dheeranupattana, S, Lowlam, J & Boonchalermkit, S 2009, 'Semisynthesis and Biological Activity of Stemofoline Alkaloids', Journal of Natural Products, vol. 72, no. 4, pp. 679-684.View/Download from: UTS OPUS or Publisher's site
The semisynthesis of the Stemona alkaloids (3?R)-stemofolenol (1), (3?S)-stemofolenol (2), methylstemofoline (3), and (3?S)-hydroxystemofoline (5) and the unnatural analogues (11E)-methylstemofoline (15) and 3?R-hydroxystemofoline (11) has been achieved starting from (11Z)-1?,2?-didehydrostemofoline (4). This synthesis allowed, for the first time, access to diastereomerically enriched samples of 1 and 2 and the assignment of their absolute configurations at C-3?. These compounds were obtained in sufficient quantities to allow for their biological testing. In a quantitative assay as AChE inhibitors, (11Z)-1?,2?-didehydrostemofoline (4) and (3?S)-hydroxystemofoline (5) were found to be the most active.
Mbere-Nguyen, U, Ung, AT & Pyne, SG 2009, 'The synthesis of carbon-linked bisbenzylisoquinolines via ruthenium- mediated olefin-metathesis', Tetrahedron, vol. 65, no. 31, pp. 5990-6000.View/Download from: UTS OPUS or Publisher's site
Novel laudanosine dinners in which two laudanosine units are linked at C-2' via a two and four-carbon linker have been prepared using ruthenium-mediated olefin-metathesis. In addition, a second four-carbon linker between the two isoquinoline N-atoms was also present leading to a novel macrocyclic ring system. Five of these compounds showed higher cytostatic activity on three cancer cell lines than thalicarpine.
Taylor, SR, Ung, AT & Pyne, SG 2007, 'The synthesis of 2 ',2 '-bis-benzylisoquinolines and their cytostatic activities', TETRAHEDRON, vol. 63, no. 45, pp. 10896-10901.View/Download from: Publisher's site
Yong, SR, Ung, AT, Pyne, SG, Skelton, BW & White, AH 2007, 'Syntheses of spiro[cyclopropane-1,3'-oxindole]-2-carboxylic acid and cyclopropa[c]quinoline-7b-carboxylic acid and their derivatives', Tetrahedron, vol. 63, no. 5, pp. 1191-1199.View/Download from: UTS OPUS or Publisher's site
The synthesis of spiro[cyclopropane-1,3?-oxindole]-2-carboxylic acid, including novel 3-(2- and 3-pyridyl)-substituted analogues and the novel cyclopropa[c]quinoline-7b-carboxylic acid and their ester and amide derivatives is described. These syntheses involve diastereoselective cyclopropanation reactions of methyl 2-(2-nitrophenyl)acrylate and (3E)-(pyridin-2-ylmethylene)- and (3E)-(pyridin-3-ylmethylene)-1,3-dihydro-2H-indol-2-one with ethyl (dimethyl sulfuranylidene) acetate (EDSA). The synthesis of methyl cyclopropa[c]quinoline-7b-carboxylate involves a regioselective reductive cyclization of a nitro-diester precursor. The relative stereochemistry of key compounds has been determined by single-crystal X-ray structural analysis.
Pyne, S.G., Ung, A.T., Jatisatienr, A. & Mungkornasawakul, P. 2007, 'The pyrido[1,2-a]azepine Stemona alkaloids', Maejo international journal of science and technology, vol. 1, no. 2, pp. 157-165.View/Download from: UTS OPUS
This paper reviews the isolation, structure elucidation, proposed biosynthesis and biological activities of the small, but increasing, number of pyrido[1,2-a]azepine Stemona alkaloids.
Taylor, SR, Ung, AT, Pyne, SG, Skelton, BW & White, AH 2007, 'Intramolecular versus intermolecular oxidative couplings of ester tethered di-aryl ethers', Tetrahedron, vol. 63, no. 46, pp. 11377-11385.View/Download from: UTS OPUS or Publisher's site
The oxidative cyclization of 3,4-dimethoxyphenyl 3,4-dimethoxyphenylacetate, through intramolecular biphenyl bond formation, was successful and gave the target seven-membered lactone in good yield (8586%). All other ester substrates gave biphenyl products or their further oxidized products via intermolecular coupling of their radical cation intermediate with the neutral substrate. It appears that matching of the oxidation potentials and nucleophilicity of the two phenyl rings, the positioning of the ring substituents and the ease of E to Z isomerization about the ester CO bond are important factors contributing to these product outcomes.
Yong, SR, Ung, AT, Pyne, SG, Skelton, BW & White, AH 2007, 'Synthesis of novel 30-spirocyclic-oxindole derivatives and assessment of their cytostatic activities', Tetrahedron, vol. 63, no. 25, pp. 5579-5586.View/Download from: UTS OPUS or Publisher's site
The synthesis of some novel 3?-spirocyclic-oxindole compounds, based on the spiro[indole-3,5?-isoxazolidin]-2(1H)-one, the 2?H-spiro[indole-3,6?-[1,3]oxazinane]-2,2?(1H)-dione and the 2?H-spiro[indoline-3,3?-pyrrolo[1,2-c][1,3?]oxazine]-1?,2(1H)-dione heterocyclic structures, is described. These compounds were prepared from methyl ?-(2-nitrophenyl)acrylate via [1,3]-dipolar cycloaddition reactions with two acyclic nitrones and one cyclic nitrone followed by reduction of the cycloadducts and then treatment with triphosgene. Two of these compounds showed significant cytostatic activity on three cancer cell lines with GI50 values of 2.64.1 ?M on the human breast cancer cell line, MCF-7.
Taylor, SR, Ung, AT & Pyne, SG 2007, 'Synthesis of benzo[c]chromen-6-ones via novel cyclic aryl-Pd(II)-ester enolate intermediates', Tetrahedron, vol. 63, no. 45, pp. 10889-10895.View/Download from: UTS OPUS or Publisher's site
The examination of the palladium catalysed arylation reactions of mono-iodo derivatives of the phenyl and benzyl esters of benzoic acid, phenylacetic acid and dehydrocinnamic acid has resulted in the formation of benzo[c]chromen-6-ones, unexpected cinnamate and succinate products and diphenyl dimers. Many of these products can be rationalised as arising from novel cyclic ArPd(II)enolate intermediates, formed by intramolecular CH activation by ArPd(II).
Sastraruji, T., Jatisatienr, A., Issakul, K., Pyne, S.G., Ung, A.T., Lie, W. & Williams, M.C. 2006, 'Phytochemical Studies on Stemona Plants: Isolation of New Tuberostemonine and Stemofoline Alkaloids', Natural product communications, vol. 1, no. 10, pp. 813-818.View/Download from: UTS OPUS
Six new stemofoline alkaloids, (2`R)-hydroxystemofoline (5), (3`R)-stemofolenol (6), (3`S)-stemofolenol (7), 1`,2`-didehydrostemofoline-N-oxide (8), the first C19 stemofoline alkaloid, methylstemofoline (9), and the first glycosidated Stemona alkaloid, stemofolinoside (10), and three known alkaloids, (2`S)-hydroxystemofoline (2), (11Z)-1`,2`-didehydrostemofoline (3), and (11E)-1`,2`-didehydrostemofoline (4), have been isolated from a root extract of an unidentified Stemona species. The structure and relative configuration of these new alkaloids have been determined by spectral data interpretation and from semisynthetic studies.
Sastraruji, T, Jatisatienr, A, Pyne, SG, Ung, AT, Lie, W & Williams, MC 2005, 'Phytochemical Studies on Stemona Plants: Isolation of Stemofoline Alkaloids', Journal of Natural Products, vol. 68, no. 12, pp. 1763-1767.View/Download from: UTS OPUS or Publisher's site
Six new stemofoline alkaloids, (2¢R)-hydroxystemofoline (5), (3¢R)-stemofolenol (6), (3¢S)-stemofolenol (7),1¢,2¢-didehydrostemofoline-N-oxide (8), the first C19 stemofoline alkaloid, methylstemofoline (9), and the first glycosidated Stemona alkaloid, stemofolinoside (10), and three known alkaloids, (2¢S)-hydroxystemofoline (2), (11Z)-1¢,2¢-didehydrostemofoline (3), and (11E)-1¢,2¢-didehydrostemofoline (4), have been isolated from a root extract of an unidentified Stemona species. The structure and relative configuration of these new alkaloids have been determined by spectral data interpretation and from semisynthetic studies.
Yong, SR, Williams, MC, Pyne, SG, Ung, AT, Skelton, BW, White, AH & Turner, P 2005, 'Synthesis of 2-azaspiro[4.4]nonan-1-ones via phosphine-catalysed [3+2]-cycloadditions', Tetrahedron, vol. 61, no. 34, pp. 8120-8129.View/Download from: UTS OPUS or Publisher's site
The phosphine-catalyzed [3+2]-cycloaddition of the 2-methylene ?-lactams 4 and 5 and the acrylate 6 with the ylides derived from the ethyl ester, the amide or the chiral camphor sultam derivative of 2-butynoic acid (7ac) give directly, or indirectly after reductive cyclization, spiro-heterocyclic products. The acid 32 underwent Curtius rearrangement and then acid hydrolysis to give two novel spiro-cyclic ketones, 41 and 42.
Ung, AT, Pyne, SG, Batenburg-Nguyen, U, Davis, AS, Sherif, A, Bischoff, F & Lesage, AS 2005, 'Synthesis and antagonist activities of 4-aryl-substituted conformationally restricted cyclopentenyl and cyclopentanyl-glutamate analogues', Tetrahedron, vol. 61, no. 7, pp. 1803-1812.View/Download from: UTS OPUS or Publisher's site
The conformationally restricted glutamate analogues, 4-aryl-1-amino-2-cyclopentene-1,3-dicarboxylates and their cyclopentane analogues have been prepared in a diastereoselective manner. Biological studies of 12a and 12b indicates that both compounds are modest antagonists at mGluR2.
Mungkornasawakul, P., Matthews, H., Ung, A.T., Pyne, S.G., Jatisatienr, A., Lie, W., Skelton, B.W. & White, A.H. 2005, 'Confirmation of the structure of oxystemokerrin by single crystal x-ray structural analysis and a proposed biosynthesis', A C G C Chemical Research Communications, vol. 19, pp. 30-33.View/Download from: UTS OPUS
Mungkornasawakul, P, Pyne, SG, Jatisatienr, A, Lie, W, Ung, AT, Issakul, K, Sawatwanich, A, Supyen, D & Jatisatienr, C 2004, 'Phytochemical studies on Stemona burkillii Prain: Two new dihydrostemofoline alkaloids', JOURNAL OF NATURAL PRODUCTS, vol. 67, no. 10, pp. 1740-1743.View/Download from: Publisher's site
Mungkornasawakul, P., Pyne, S.G., Jatisatienr, A., Lie, W., Ung, A.T., Issakul, K., Sawatwanich, A., Supyen, D. & Jatisatienr, C. 2004, 'Phytochemical Studies on Stemona burkillii Prain: Two New Dihydrostemofoline Alkaloids', Journal of Natural Products, vol. 67, no. 10, pp. 1740-1743.View/Download from: UTS OPUS or Publisher's site
Two new dihydrostemofoline alkaloids, 11(S),12(R)-dihydrostemofoline (3) and stemoburkilline (4), along with stemofoline (1) and 2`-hydroxystemofoline (2) have been isolated from a root extract of Stemona burkillii Prain. The structure and relative configuration of 3 have been determined via spectroscopic data and from comparison with synthetic 11(S),12(S)-dihydrostemofoline (5). The configuration of the exo-cyclic alkene group in 4 is tentively assigned as E on the basis of mechanistic considerations.
Mungkornasawakul, P, Pyne, SG, Jatisatienr, A, Supyen, D, Jatisatienr, C, Lie, W, Ung, AT, Skelton, BW & White, AH 2004, 'Phytochemical and Larvicidal Studies on Stemona curtisii: Structure of a New Pyrido[1,2-a]azepine Stemona Alkaloid', Journal of Natural Products, vol. 67, no. 4, pp. 675-677.View/Download from: UTS OPUS or Publisher's site
A new pentacyclic Stemona alkaloid, stemocurtisinol (3), with a pyrido[1,2-a]azepine A,B-ring system, and the known pyrrolo[1,2-a]azepine alkaloid oxyprotostemonine (4) have been isolated from a root extract of S. curtisii. The structure and relative stereochemistry of stemocurtisinol was determined by spectral data interpretation and X-ray crystallography. This compound is a diastereoisomer of oxystemokerrin and has the opposite configuration at C-4 and C-19. The individual alkaloid components showed significant larvicidal activity (IC50 4-39 ppm) on mosquito larvae (Anopheles minimus HO).
Mungkornasawakul, P., Pyne, S.G., Jatisatienr, A., Supyen, D., Lie, W., Ung, A.T., Skelton, B.W. & White, A.H. 2003, 'Stemocurtisine, the first pyrido[1,2-a]azapine Stemona alkaloid. (vol 66, pg 980, 2003)', JOURNAL OF NATURAL PRODUCTS, vol. 66, no. 10, pp. 1404-1404.View/Download from: Publisher's site
Mungkornasawakul, P, Pyne, SG, Jatisatienr, A, Supyen, D, Lie, W, Ung, AT, Skelton, BW & White, AH 2003, 'Stemocurtisine, the First Pyrido[1,2-a]azapine Stemona Alkaloid', Journal of Natural Products, vol. 66, no. 7, pp. 980-982.View/Download from: UTS OPUS or Publisher's site
A new pentacyclic stemona alkaloid, stemocurtisine (2), with a novel pyrido[1,2-a]azapine A,B-ring system, has been isolated from a root extract of Stemona curtisii. The structure and relative stereochemistry was determined by spectral data interpretation and X-ray crystallography
Ung, AT, Schafer, K, Lindsay, KB, Pyne, SG, Amornraksa, K, Wouters, R, Van der Linden, I, Biesmans, I, Lesage, AS, Skelton, BW & White, AH 2002, 'Synthesis and Biological Activities of Conformationally Restricted Cyclopentenyl-Glutamate Analogues', Journal of Organic Chemistry, vol. 67, pp. 227-233.View/Download from: Publisher's site
Alshahateet, SF, Bishop, R, Craig, DC, Scudder, ML & Ung, AT 2001, 'Pseudopolymorphic Clathrate Structures Formed by an Alicyclic Dialcohol Inclusion Host1', Structural Chemistry, vol. 12, pp. 251-257.View/Download from: Publisher's site
Jeoffreys, GR, Ung, AT, Pyne, SG, Skelton, BW & White, AH 1999, 'Synthesis of thiazole analogues of the immunosuppressive agent (1R,2S,3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole', Journal of the chemical chemistry. Perkin transactions 1, vol. 16, pp. 2281-2291.
Bishop, R, Craig, DC, Dance, IG, Scudder, ML & Ung, AT 1999, 'Interpenetrating inclusion lattices: comparison of the B-hydroquinone and ellipsoidal clathrate structures R', Journal of Structural Chemistry, vol. 40, no. 5, pp. 663-671.View/Download from: UTS OPUS or Publisher's site
Crystallization of 2,7-dimethyltricyclo[43.1.13,8]undecane-syn-2,syn-7-diol 2 from acetonitrile or dichloro-methane yields the compounds (2)4-(guest) in space group 141/acd which are further examples of the ellipsoidal clathrate structure. Both enantiomers of 2 are linked through (O-H)4 cycles of hydrogen bonds to form a three-dimensional sublattice. Two inversion related sublattices interpenetrate thereby generating a superlattice with guest-occupied voids situated between the two individual sublattices. The two X-ray structures are compared and contrasted with that of Powells (hydroquinone)3 (SO2) clathrate compound.
Pyne, SG & Ung, AT 1998, 'Diastereoselective Synthesis of (1S,2S,3R)- and (1R,2R,3R)-2-acetyl-5-(1,2,3,4-tetrahydroxybutyl) thiazole', SYNLETT, no. 3, pp. 280-282.
Ung, A.T. & Pyne, S.G. 1998, 'Diastereoselective synthesis of (1S,2S,3R)- and (1R,2R,3R)-2-acetyl-5-(1,2,3,4-tetrahydroxybutyl)thiazole', Synlett, vol. 9, pp. 1395-1407.
Ung, A.T., Pyne, S.G., Skelton, B.W. & White, A.H. 1996, 'Asymmetric Synthesis of (1R, 2S, 3R)-2-Acetyl-5-(1,2,3,4- tetrahydroxybutyi)thiazole', Tetrahedron, vol. 52, no. 44, pp. 14069-14078.View/Download from: UTS OPUS or Publisher's site
A method for preparing the thiazole analogue 2 of the biologically active compound (1R, 2S, 3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole 1 is reported.
Ung, A.T. & Pyne, S.G. 1996, 'Synthesis Of Fluorescent And Biotinylated Analogues Of (Ir, 2s, 3r)-2.Acetyl-4(5)-(1,2,3,4-Tetrahydroxybutyl)Imidazole', Tetrahedron letters, vol. 37, no. 34, pp. 6209-6212.View/Download from: UTS OPUS or Publisher's site
A method for preparing fluorescent and biotinylated analogues of the biologically active compound (1R, 2S, 3R)-2-acetyl-4(5)-(1,2,3,4-tetrahydroxybutyl)imidazole 1 is reported
Bishop, R, Craig, DC, Dance, I, Gizachew, D, Scudder, ML & Ung, AT 1996, 'Helical tubulate inclusion compounds: size, shape, and stoichiometry', Molecular Crystals and Liquid crystals, vol. 278, pp. 65-76.
Ung, AT, Bishop, R, Craig, DC, Dance, I, Gizachew, D & Scudder, ML 1995, 'Structure and Analysis of Helical Tubulate Inclusion Compounds Formed by 2,6-Dimethylbicyclo[ 3.3.l]nonane-exo-2,exo-6-diol', Journal of the American Chemical Society, vol. 117, pp. 8745-8756.View/Download from: Publisher's site
Ung, AT, Bishop, R, Craig, DC, Dance, I & Scudder, ML 1994, 'Formation and Structure of a New Family of Organic Cocrystals', Chemistry of Materials, vol. 6, pp. 1269-1281.View/Download from: Publisher's site
Bishop, R, Craig, DC, Dance, I, Scudder, ML & Ung, AT 1994, 'Helical tubuland diol-phenol co-crystals', Molecular Crystals and Liquid crystals, vol. 240, pp. 113-119.
UNG, A.T., BISHOP, R., CRAIG, D.C., DANCE, I.G. & SCUDDER, M.L. 1993, 'PREDICTION AND STRUCTURE OF POLYMORPHIC LATTICE INCLUSION-COMPOUNDS OF 2,7-DIMETHYLTRICYCLO[184.108.40.206(3,8)]UNDECANE-SYN-2,SYN-7-DIOL', TETRAHEDRON, vol. 49, no. 3, pp. 639-648.View/Download from: Publisher's site
UNG, AT, BISHOP, R, CRAIG, DC, DANCE, IG, RAE, AD & SCUDDER, ML 1993, 'HELICAL TUBULATE INCLUSION-COMPOUNDS OF FERROCENE AND SQUALENE', JOURNAL OF INCLUSION PHENOMENA AND MOLECULAR RECOGNITION IN CHEMISTRY, vol. 15, no. 4, pp. 385-398.View/Download from: Publisher's site
Ung, AT, Bishop, DC, Craig, DC, Dance, IG & Scudder, ML 1993, 'Helical tubulate inclusion compounds', Supramolecular chemistry, vol. 2, pp. 123-131.
Ung, AT, Bishop, R, Craig, DC, Dance, I & Scudder, ML 1993, 'Prediction and Structure of Polymorphic Lattice Inclusion Compounds of 2,7-Dimethyltricyclo[4.3.1.03,8]undecanesyn- 2,syn-7-diol', Tetrahedron, vol. 49, no. 3, pp. 639-648.View/Download from: UTS OPUS
The host molecule 2,7-drmethylmcyclo[4 3 1 03~a]undecane-syn-2,rysyn-7-diol 1 is known to fotm two d&rent structural types of latuce mcluaon compound dependent on the guest molecule chosen Guests, mcludmg 1,Zdlchlorobenzene 2, have now been predicted which result in the formation of both lattice types according to the crystallisation conditions employed. Crvstal structures of the ellpsoidal clathrate type. (Racemic-1)4.( 1.2- chlorobenzene), space group I41/acd; and the helical tubulate hype `(Resolved-1)3 (1,2-Dichlorobenzene), space group P3121 are presented The latter polymorph 1s transformed into the former on heating in a sealed system
Ung, A.T., Bishop, R., Craig, D.C., Dance, I. & Scudder, M.L. 1993, 'Helical Tubulate Inclusion Compounds of Ferrocene and Squalene', Journal of Inclusion Phenomena and Molecular Recognition in Chemistry, vol. 2, pp. 123-131.
Bishop, R., Craig, D.C., Dance, I., Scudder, M.L. & Ung, A.T. 1993, 'Helical tubulate inclusion compounds', Supramolecular chemistry, vol. 2, pp. 123-131.
Ung, AT, Bishop, R, Craig, DC, Dance, IG & Scudder, ML 1993, 'Crystal engineering: helical tubuland diol-phenol co-crystrals', Journal of the Chemical Society, Chemical Communications, vol. 3, pp. 322-323.
Bishop, R, Craig, DC, Dance, I, Scudder, ML & Ung, AT 1992, 'Formation and stability of the helical tubuland diol inclusion lattice', Molecular Crystals and Liquid crystals, vol. 211, pp. 141-146.
Ung, AT, Bishop, R, Craig, DC, Dance, ML & Scudder, ML 1992, 'Crystal structures of helical tubulatr inclusion compounds formed by 2,6=dimethylbicyclo (3.3.1)nonane-exo-2, exo-6-diol', Royal Chemical Society. Journal. Perkin Transactions 2, vol. 6, pp. 861-862.
Ung, AT, Bishop, R, Craig, DC, Dance, IG, Scudder, ML & Yunus, J 1992, 'Ritter reactions. VII. ?Diverse reactivity of the 3-azatricycle[5.3.1.04,9]undec-2-ene system with dimethyl acetylenedicarboxylate', Australian Journal Of Chemistry, vol. 45, pp. 553-565.View/Download from: Publisher's site
UNG, A.T., SCUDDER, M.L., DANCE, I.G. & BISHOP, R. 1991, 'GUEST CONTROL OF DIOL INCLUSION HOST LATTICES', ABSTRACTS OF PAPERS OF THE AMERICAN CHEMICAL SOCIETY, vol. 201, pp. 327-ORGN.
Ung, AT, Bishop, R, Craig, DC, Dance, I & Scudder, ML 1991, 'Stability of the helical tubuland inclusion lattice', Journal of the chemical society, vol. 15, pp. 1012-1014.
Palee, J., Dheeranupattana, S., Jatisatienr, A., Jatisatienr, C., Pyne, S.G., Ung, A.T. & Sastraruji, T. 2008, 'Effects of methyl jasmonate on alkaloid production in callus culture of Stemona curtisii Hook.f', PLANTA MEDICA, pp. 1162-1162.
Chotikadachanaron, K., Dheeranupattana, S., Jatisatienr, A., Jatisatienr, C., Pyne, S.G., Ung, A.T. & Sastraruji, T. 2008, 'Secondary compound production in root cultures of Stemona curtisii Hook. f', PLANTA MEDICA, pp. 1166-1166.
Sastraruji, T., Kotabin, N., Jatisatienr, C., Dheeranupattana, S., Pyne, S.G. & Ung, A.T. 2008, 'Phytochemical studies on Stemona plants: biological activities of some stemofoline alkaloids', PLANTA MEDICA, pp. 985-985.
Pyne, SG, Jatisatienr, A, Mungkornasawakul, P, Ung, AT, Limtrakul, P, Sastraruji, T, Sastraruji, K, Chaiyong, S, Umsumarng, S, Baird, MC, Dau, XD & Ramli, RA 2017, Phytochemical, synthetic and biological studies on Stemona and Stichoneuron plants and alkaloids: A personal perspective, pp. 1365-1369.
This report is an overview of our research on phytochemical, synthetic and biological studies of the Stemona and Stichoneuron species of plants.
Using the crystal structure of S. aureus FtsZ with a co-crystallised known inhibitor, a pharmacophore was developed that could be utilized in the design of novel inhibitors. A library of 19 molecules were synthesized and structurally elucidated that contain a pyrazole linker (Scheme 1). These molecules were screened against S. aureus ATCC 25923 and Escherichia coli (E. coli) MG1556 cells to determine their antibacterial activity.
The alkaloid class of natural compounds is extensively known for their variety of biological activities. A high percentage of currently employed chemotherapeutic drugs - more than 60% for cancer are of plant origin, and many are alkaloids. Synthetic compounds that display similar structures to alkaloids are known as alkaloid-like molecules. Alkaloids are commonly documented to poses pharmacological properties such as antineoplasticity and acetylcholinesterase (AChE) inhibition. The Aristotelia alkaloids (1 and 2) have a broad spectrum of biological activities, several of which contain the same 3-aza-bicyclo[3.3.1]nonane core structure architecture, seen in blue in Figure 2.
Figure 1: Aristotelia alkaloids, 1 and 2.
As these Alkaloids are both rare and require complex isolation, it is more resourceful to generate libraries of molecules with the same core scaffold through synthetic pathways, such as the Bridging Ritter reaction. Through the use of the Bridging Ritter reaction with (-)--pinene (3) and various nitriles, a small library of alkaloid-like molecules has been synthesized.
Figure 2: The bridging Ritter reaction of (-)--pinene with various nitriles.
AChE inhibitors are currently the front line of drugs used for relieving the symptoms of Alzheimer's disease (AD) by restoring natural levels neurotransmitter acetylcholine, found to be low in the synapse of AD suffers. All of the currently approved AChE inhibitors have severe undesirable side-effects and with the diseases mortality rate expected to increase greatly, it is imperative that more suitable drug candidates be developed. Therefore, these alkaloid-like compounds were screened for AChE inhibitory activity using The TLC bioautographic method and Ellman Assay.
A library of 27 alkaloid-like molecules has been synthesised. The library is currently undergoing in-house anticancer testing using the MTS assay against the MDA-MB-231 breast cancer cell line. External screening has...
Xu, X. & Ung, A.T. 2016, 'Alkaloid-like compounds as anti-cancer agents and potential AChE inhibitors'.
Alkaloids are a natural occurring, structurally diverse group of compounds. They are found in bacteria, fungi, plants and animals. They are also historically known for their medicinal benefits and can exhibit a broad range of biological activities, including anti-cancer, anti-bacterial, as well as the ability to inhibit acetylcholinesterase enzyme (AChE), which is used in the treatment of Alzheimer's disease (AD).1,2 Natural alkaloids and the analogues derived from them are to date the most successful anticancer drugs on the market, and many more under clinical trials. These alkaloid derived drugs continue to play a significant role in the discovery of anti-cancer agents.
Due to the limited resources of these natural alkaloids, it is more feasible to synthesise these compounds via the Bridging Ritter Reaction to investigate their possible anti-cancer as well as potential AChE inhibiting activities (Scheme 1).
A library of 33 alkaloid-like molecules has been synthesised and was screened against breast cancer cell line MCF-7 and MDA-MB-231, as well as for their AChE inhibitory activity using The Ellman Assay.3 Screening has revealed a series of compounds that are active against the cancer cell line tested. The recent finding of our work will be presented in detailed in this presentation.
the process of neurotransmission across the synaptic cleft in neurons. Reversible AChE inhibitors are currently marketed for the treatment of Alzheimer's disease for their ability to slow down the progression of symptom development such as memory loss. An example of a current treatment is Galantamine (Reminyl), an alkaloid derived from the Galanthus Nivalis species2.
Enantiomers of (-)-2 and (-)-3were successfully prepared and screened for AChE inhibitory activity, along with a small library of novel compounds not observed in previous work. Furthermore, the influence of solvent choice was investigated between (R)-limonene and various nitriles under the Bridging Ritter reaction conditions. The concluding results from this project will be presented.
The alkaloid class of natural compounds is extensively known for their variety of biological activities. A high percentage of currently employed chemotherapeutic drugs - more than 60% for cancer are of plant origin, and many are alkaloids. Synthetic compounds that display similar structures to alkaloids are known as alkaloid-like molecules. Alkaloids are commonly documented to poses pharmacological properties such as acetylcholinesterase (AChE) inhibitory and antineoplasticity. The Aristotelia alkaloids (1, 2, 3) have a broad spectrum of biological activities, several of which contain the same 3-aza-bicyclo[3.3.1]nonane (4) core structure architecture. As these Alkaloids are both rare and require complex isolation, it is more resourceful to generate libraries of molecules with the same core scaffold through synthetic pathways, such as the Bridging Ritter reaction. Through the use of the Bridging Ritter reaction with (-)--pinene (5) and various nitriles, a small library of alkaloid-like molecules has be synthesized and purified. Their activity against AChE is then tested.
AChE inhibitors are currently the front line of drugs used for relieving the symptoms of Alzheimer's disease (AD). Through reducing the natural decomposition of the neurotransmitter acetylcholine (ACh) by AChE, in the synapse of AD suffers, cognitive function lost due to decreased levels of ACh can be restored. There are currently only three AChE inhibitors approved for use in Australia, all of which are not without undesirable side-effects. With the mortality rate reported to be 11,000 people in Australia alone in 2013, and that number expected to increase as the baby boomer generation enters the age bracket in which most people develop the disease.
A library of 27 alkaloid-like molecules has been synthesised and tested using the TLC bioautographic method for initial rapid screening. The IC50 values of the inhibitors were determined using the Ellman Assay. The recent findin...