title: Synthesis and antitubercular activity of monocyclic nitroimidazoles: insights from econazole.
abstract: We have designed and synthesized econazole-derived nitroimidazoles to investigate the antitubercular activity of the nitroimidazole compounds. The introduction of a nitro group at the 4-position of the imidazole on econazole abolished the antitubercular activity. However, alcoholic nitroimidazoles 4 and 6 compounds were active against Mycobacterium tuberculosis (Mtb). While the MIC value of econazole was 16 μg/mL, the MIC of 6a and 6f turned out to be 0.5 μg/mL. In particular, the activity of 6f against non-replicating Mtb was as good as PA-824, which is currently in clinical phase II studies as an antitubercular agent. Overall, alcohol compounds 4 and 6 tend to be more active than ether compounds 5 and 7.
authors.affiliation: Cancer & Infectious Diseases Research Center, Korea Research Institute of Chemical Technology, Daejeon, Republic of Korea.
authors.forename: Sang-Ho
authors.initials: SH
authors.lastname: Lee
authors.forename: Suhyun
authors.initials: S
authors.lastname: Kim
authors.forename: Min-Han
authors.initials: MH
authors.lastname: Yun
authors.forename: Yong Sup
authors.initials: YS
authors.lastname: Lee
authors.forename: Sang-Nae
authors.initials: SN
authors.lastname: Cho
authors.forename: Taegwon
authors.initials: T
authors.lastname: Oh
authors.forename: Pilho
authors.initials: P
authors.lastname: Kim
mesh_terms: D000935:Antifungal Agents / Q000138:chemical synthesis / Q000494:pharmacology; D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D003500:Cyclization; D015195:Drug Design; D004464:Econazole / Q000737:chemistry* / Q000494:pharmacology; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009593:Nitroimidazoles / Q000138:chemical synthesis* / Q000494:pharmacology
chemical_list: D000935:Antifungal Agents; D000995:Antitubercular Agents; D009593:Nitroimidazoles; D004464:Econazole