The Davis Research Group focuses on the semi-synthesis of discovery libraries based on unique natural product scaffolds that have been isolated from Australian fungi, plants and marine invertebrates [1-4]. The ultimate goal of such libraries is to assist in the identification of bioactive compounds that can impact drug discovery or chemical biology research. This approach builds upon the chemical diversity and uniqueness found in natural products and results in the generation of small screening libraries (typically 10–20 analogues per scaffold) that allows for the rapid elucidation of both structure–activity relationships and in vitro metabolic stability, whilst circumventing the initial need for total synthesis. All analogues made during this program are added to the Davis Open-Access Natural Product Library (currently 512 pure compounds), which is curated by Compounds Australia (CA) – a national compound management facility that is housed at Griffith University and which enables dispatch of compounds to collaborators for screening against various disease and chemical biology targets [5]. This presentation will describe a number of recent semi-synthetic projects that have resulted in the discovery of new compounds that perturb various biological systems.
References
[1] E. C. Barnes, R. Kumar, R. A. Davis. Nat. Prod. Rep. 2016, 33, 372.
[2] F. A. Egbewande, N. Nilsson, J. White, M. Coster, R. A. Davis. Bioorg. Med. Chem. Lett. 2017, 27, 3185.
[3] R. Kumar, M. C. Sadowski, C. Levrier, C. C. Nelson, A. J. Jones, J. P. Holleran, V. M. Avery, P. C. Healy, R. A. Davis. J. Nat. Prod. 2015, 78, 914–918.
[4] E. C. Barnes, V. Choomuenwai, K. Andrews, R. J. Quinn, R. A. Davis Org. Biomol. Chem. 2012, 10, 4015.
[5] B. Zulfiqar, A. J. Jones, M. L. Sykes, T. B. Shelper, R. A. Davis, V. M. Avery Molecules, 2017, 22, 1715.