Rethinking Natural Products as a Source of Drug Leads
Tuesday, January 22, 2008
Presented By
Presented by Biochemical Pharmacology Discussion Group and the the American Chemical Society's New York Section
Organizers: Takushi Kaneko, TB Alliance and Vincent Gullo, Drew University
Join us as we examine the recent advances and future challenges in natural product chemistry. This symposium will address the evolution of natural product chemistry, in terms of unexplored sources of producing organisms, heterologous expression systems, and improved analytical/isolation methods.
Agenda
- 1:00 pm
Introduction and Symposium Theme
Takushi Kaneko, PhD, TB Alliance
Vincent Gullo, PhD, Drew University - 1:15 pm
Developing a Drug-Like Natural Product Screening Library
Ronald J. Quinn, PhD, Eskitis Institute, Griffith University, Brisbane, Australia - 2:00 pm
Pathways for Natural Product Drug Discovery
Guy T. Carter, PhD, Wyeth Research - 2:45 pm
Coffee Break - 3:05 pm
Turning the Tide of Natural Products Drug Discovery –
Marine Microorganisms as a Source for New Drug Leads
Ray Lam, PhD, Nereus Pharmaceuticals Inc. - 3:50 pm
Novel Approaches for Antibiotic Discovery:
Discovery of Platensimycin and Platencin
Sheo B. Singh, PhD, Merck Research Laboratories - 4:35 pm
80 Great Years of Microbial Natural Products;
Is There a Future?
Arnold L. Demain, PhD, Drew University - 5:20 pm
Wrap-Up/Discussion
Abstracts
Developing a Drug-Like Natural Product Screening Library
Ronald J Quinn
Eskitis Institute, Griffith University, Brisbane, Australia
Modern drug discovery is based in large part on high throughput screening of small molecules against macromolecular disease targets. Current thinking in the generation of drug leads embodies the concept of achieving high molecular diversity within the boundaries of reasonable drug-like properties. Molecular screening libraries should contain drug-like or lead-like compounds.
Over millions of years of evolutionary pressure, natural products have been synthesised by biosynthetic enzymes. Natural products are privileged structures due to their recognition of biology space (protein surfaces).
We have recently discovered a correlation between the biosynthetic enzymes synthesising a particular natural product and the therapeutic target of the compound. This newest correlation provides the underlying reason why natural products are validated starting points for drug design and library development. 1-3.
We have analyzed known natural products for drug-like and lead-like properties. With this information in hand, we have established a strategy to screen drug-like or lead-like fractions. Our work has demonstrated that natural products extracts can be tuned into a lead-like or drug-like library by a combination of isolation and computational methods. This information has been instrumental in developing high throughput screening strategies for natural substances.
1) McArdle, B. M.; Campitelli, M. R.; Quinn, R. J., J. Nat. Prod. 2006, 69, 14-17.
2) McArdle, B. M., Quinn, R.J. ChemBioChem, 2007, 8, 788-798
3) Mitchell, J.K.; Pitcher, D.; McArdle, B.M.; Alnefelt, T.; Duffy, S.; Avery, V.; Quinn, R.J., Bioorg. Med. Chem. Lett. 2007, 17, 6521–6524.
Pathways for Natural Product Drug Discovery
Guy T. Carter, Wyeth Research
Natural products have historically been rich sources of biologically active compounds for drug discovery. This was particularly apparent during the so-called "golden age of antibiotics discovery" that occurred during the 1940's