title: 3-benzylidene-4-chromanones: a novel cluster of anti-tubercular agents.
abstract: In a quest for developing novel anti-tubercular agents, a series of 3-benzylidene-4-chromanones 1a-l were evaluated for growth inhibition of Mycobacterium tuberculosis H37Rv. Three promising compounds 1d, g, j emerged as the lead compounds with the IC50 and IC90 values of less than 1 µg/mL. Evaluation of the potent compounds 1d, g, j and k against Vero monkey kidney cells revealed that these compounds are far more toxic to M. tuberculosis than to Vero cells. Structure-activity relationships demonstrated that 3-benzylidene-4-chromanones are more potent against M. tuberculosis than the related 2-benzylidene cycloalkanones and the meta substituted chromanone derivatives are more active than their ortho- and para-counterparts. Some guidelines for amplifying the project are presented.
authors.affiliation: Drug Discovery and Development Research Group, College of Pharmacy and Nutrition, University of Saskatchewan , Saskatoon, Saskatchewan , Canada .
authors.forename: Umashankar
authors.initials: U
authors.lastname: Das
authors.forename: Tamas
authors.initials: T
authors.lastname: Lorand
authors.forename: Stephen G
authors.initials: SG
authors.lastname: Dimmock
authors.forename: Pal
authors.initials: P
authors.lastname: Perjesi
authors.forename: Jonathan R
authors.initials: JR
authors.lastname: Dimmock
mesh_terms: D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D001597:Benzylidene Compounds / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D002867:Chromones / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D055808:Drug Discovery; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D014709:Vero Cells
chemical_list: D000995:Antitubercular Agents; D001597:Benzylidene Compounds; D002867:Chromones
keywords: 4-chromanones; anti-mycobacterial; anti-tubercular; structure–activity relationships; tuberculosis; unsaturated ketones