Evolving medicinal chemistry strategies in antibiotic discovery.
Chemical modification of synthetic or natural product antibiotic scaffolds to expand potency and spectrum and to bypass mechanisms of resistance has dominated antibiotic drug discovery and proven immensely successful. However, the inexorable evolution of drug resistance coupled with a drought in innovation in antibiotic discovery contribute to a dearth of new drugs entering to market. Better understanding of the physicochemical properties of antibiotic chemical space is required to inform new antibiotic discovery. Innovations such as the development of antibiotic adjuvants to preserve efficacy of existing drugs together with expanding antibiotic chemical diversity through synthetic biology or new techniques to mine antibiotic producing organisms, are required to bridge the growing gap between the need for new drugs and their discovery.
Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Andrew C
AC
Pawlowski
Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada.
Jarrod W
JW
Johnson
Michael G. DeGroote Institute for Infectious Disease Research and the Department of Biochemistry and Biomedical Sciences, McMaster University, Hamilton, Ontario, Canada. Electronic address: wrightge@mcmaster.ca.
Gerard D
GD
Wright
D000818:Animals; D000900:Anti-Bacterial Agents / Q000302:isolation & purification* / Q000627:therapeutic use; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification / Q000627:therapeutic use; D002626:Chemistry, Pharmaceutical / Q000379:methods* / Q000639:trends*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D058615:Synthetic Biology / Q000379:methods / Q000639:trends
D000900:Anti-Bacterial Agents; D001688:Biological Products