Recent developments in antibacterial drug discovery: microbe-derived natural products--from collection to the clinic.
The pharmaceutical industry has historically relied on nature to provide compounds for antibacterial drug discovery. In recent years, several pharmaceutical companies have scaled back their efforts in natural product research. Nevertheless, the screening of natural products for antibacterial activity continues to provide excellent sources of biologically and chemically informative leads for new drugs. New technologies in high-throughput cultivation, genetic approaches to biodiversity and discovery of relatively untapped sources of natural products are expanding the ability to find novel, potent and highly selective antibacterial structures. Advances in purification, dereplication and structure elucidation, combined with the ability to chemically or biologically derivatise hits, aim to make the timeline for natural product-derived drug discovery similar or shorter than that expected for small synthetic molecules. This review addresses the strengths and shortcomings of technologies focused on microbe-derived natural products for antibacterial drug discovery and stresses the need for commitment to these approaches in order to achieve the goal of delivering safe, efficacious and high-quality medicines in the long run.
Leeds
Jennifer A
JA
Infectious Diseases Area, Novartis Institutes for BioMedical Research, Cambridge, MA 02139, USA. jennifer.leeds@novartis.com
Schmitt
Esther K
EK
Krastel
Philipp
P
D000818:Animals; D000900:Anti-Bacterial Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001685:Biological Factors / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D004353:Drug Evaluation, Preclinical; D015507:Drugs, Investigational / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D006801:Humans; D013678:Technology, Pharmaceutical / Q000379:methods / Q000639:trends*
D000900:Anti-Bacterial Agents; D001685:Biological Factors; D015507:Drugs, Investigational