title: Next-generation antimicrobials: from chemical biology to first-in-class drugs.
abstract: The global emergence of multi-drug resistant bacteria invokes an urgent and imperative necessity for the identification of novel antimicrobials. The general lack of success in progressing novel chemical entities from target-based drug screens have prompted calls for radical and innovative approaches for drug discovery. Recent developments in chemical biology and target deconvolution strategies have revived interests in the utilization of whole-cell phenotypic screens and resulted in several success stories for the discovery and development novel drug candidates and target pathways. In this review, we present and discuss recent chemical biology approaches focusing on the discovery of novel targets and new lead molecules for the treatment of human bacterial and protozoan infections.
authors.affiliation: Lee Kong Chian School of Medicine and School of Biological Sciences, Nanyang Technological University, 30 Biopolis Street, #B2-15a, Singapore, 138671, Singapore. michelle.ang@ntu.edu.sg.
authors.forename: Michelle Lay Teng
authors.initials: ML
authors.lastname: Ang
authors.affiliation: Global Health Institute, Swiss Federal Institute of Technology in Lausanne (EPFL), 1015, Lausanne, Switzerland.
authors.forename: Paul
authors.initials: P
authors.lastname: Murima
authors.affiliation: Lee Kong Chian School of Medicine and School of Biological Sciences, Nanyang Technological University, 30 Biopolis Street, #B2-15a, Singapore, 138671, Singapore. kevin.pethe@ntu.edu.sg.
authors.forename: Kevin
authors.initials: K
authors.lastname: Pethe
mesh_terms: D000818:Animals; D000890:Anti-Infective Agents / Q000737:chemistry* / Q000627:therapeutic use*; D020808:Central Nervous System Protozoal Infections / Q000188:drug therapy / Q000378:metabolism; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D055808:Drug Discovery / Q000379:methods*; D006801:Humans; D009169:Mycobacterium tuberculosis / Q000187:drug effects / Q000378:metabolism
chemical_list: D000890:Anti-Infective Agents
keywords: Antimicrobials; Chemical biology; Drug discovery; First-in-class drugs; Lead optimization; Screening