title: Modification of existing antibiotics in the form of precursor prodrugs that can be subsequently activated by nitroreductases of the target pathogen.
abstract: The use of existing antibiotics in the form of prodrug followed by activation using enzymes of pathogenic origin could be a useful approach for antimicrobial therapy. To investigate this idea, a common antibiotic, sulfamethoxazole has been redesigned in the form of a prodrug by simple functional group replacement. Upon reductive activation by a type I nitroreductase from a pathogen, the drug displayed enhanced antimicrobial capacity. This strategy could improve the efficacy and selectively of antibiotics and reduce the incidence of resistance.
authors.affiliation: Department of Chemistry, Gebze Technical University, Cayirova Campus, Gebze-Kocaeli, 41400, Turkey. Electronic address: ayhancelik@gtu.edu.tr.
authors.forename: Ayhan
authors.initials: A
authors.lastname: Çelik
authors.affiliation: Department of Chemistry, Gebze Technical University, Cayirova Campus, Gebze-Kocaeli, 41400, Turkey.
authors.forename: Gülden
authors.initials: G
authors.lastname: Yetiş
authors.affiliation: Department of Chemistry, Canakkale 18 Mart University, Terzioğlu Campus, 17100 Çanakkale, Turkey.
authors.forename: Mehmet
authors.initials: M
authors.lastname: Ay
authors.affiliation: Department of Chemistry, Canakkale 18 Mart University, Terzioğlu Campus, 17100 Çanakkale, Turkey.
authors.forename: Tuğba
authors.initials: T
authors.lastname: Güngör
mesh_terms: D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D052978:Disk Diffusion Antimicrobial Tests; D024881:Drug Resistance, Bacterial / Q000187:drug effects; D007700:Kinetics; D009601:Nitroreductases / Q000737:chemistry / Q000378:metabolism*; D011355:Prodrugs / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013056:Spectrophotometry, Ultraviolet; D013210:Staphylococcus / Q000187:drug effects; D013420:Sulfamethoxazole / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology
chemical_list: D000900:Anti-Bacterial Agents; D011355:Prodrugs; D009601:Nitroreductases; D013420:Sulfamethoxazole
keywords: Nitroreductase; Prodrugs; Sulfamethoxazole