title: 7-Hydroxy-(E)-3-phenylmethylene-chroman-4-one analogues as efflux pump inhibitors against Mycobacterium smegmatis mc² 155.
abstract: Efflux pump (EP) induces resistance in mycobacteria and hence could be explored as a new target for the discovery of anti-TB agents. In search for efflux pump inhibitors from natural products, bonducellin, a homoisoflavonoid was isolated from Caesalpinia digyna roots and evaluated for modulation and EP inhibitory activity. Bonducellin showed modulation in the MIC of EtBr by eight fold at a concentration of 62.5 mg/L and also showed significant EP inhibitory activity. A synthetic scheme was designed to prepare analogues of 7-hydroxy-(E)-3-phenylmethylene-chroman-4-one by modification at the phenylmethylene-ring and the synthesized compounds were evaluated in accumulation and efflux assays. Analogues 1, 7-11, 13-15, 17 and 19 were found to be good modulators and decreased the MIC of EtBr by ≥4 fold at sub-inhibitory concentration. The compounds 8, 13 and 17 were the most potent inhibitors of ethidium bromide efflux in Mycobacterium smegmatis mc(2) 155.
authors.affiliation: Department of Natural Products, National Institute of Pharmaceutical Education and Research, Sector-67, SAS Nagar, Mohali 160062, Punjab, India.
authors.forename: Somendu K
authors.initials: SK
authors.lastname: Roy
authors.forename: Neela
authors.initials: N
authors.lastname: Kumari
authors.forename: Shiv
authors.initials: S
authors.lastname: Gupta
authors.forename: Sonika
authors.initials: S
authors.lastname: Pahwa
authors.forename: Hemraj
authors.initials: H
authors.lastname: Nandanwar
authors.forename: Sanjay M
authors.initials: SM
authors.lastname: Jachak
mesh_terms: D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000494:pharmacology*; D002839:Chromans / Q000737:chemistry* / Q000494:pharmacology*; D002867:Chromones / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects*; D008826:Microbial Sensitivity Tests; D020102:Mycobacterium smegmatis / Q000187:drug effects*; D013329:Structure-Activity Relationship
chemical_list: C586655:7-hydroxy-(E)-3-phenylmethylene-chroman-4-one; D000900:Anti-Bacterial Agents; D002839:Chromans; D002867:Chromones
keywords: Bonducellin; Caesalpinia digyna; Efflux pump; Homoisoflavonoid