title: Three-component, one-pot synthesis of anthranilamide Schiff bases bearing 4-aminoquinoline moiety as Mycobacterium tuberculosis gyrase inhibitors.
abstract: An efficient three-component, one-pot protocol is described for the synthesis of biologically interesting 2-(benzylideneamino)-N-(7-chloroquinolin-4-yl)benzohydrazide derivatives from isatoic anhydride, 7-chloro-4-hydrazinylquinoline and aromatic and/or hetero aromatic aldehydes under catalyst free condensation by using water as reaction media. All synthesized compounds were evaluated for their antimycobacterial activity against Mycobacterium tuberculosis (MTB) and cytotoxicity activity against normal VERO cell lines. The synthesized compounds exhibited minimum inhibitory concentration (MIC) ranging from 0.78 to 25μM. Among the tested compounds 4c, 4o, 4r, and 4u exhibited promising inhibitory activity (MIC=3.12μM). Compounds 4h and 4i stand out, showing MIC values of 0.78 and 1.56μM respectively. Both compounds were further screened for their Mycobacterium tuberculosis DNA gyrase inhibitory assay which suggested that these compounds have a great potential for further optimization and development as antitubercular agents.
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Nehrunagar, Belagavi 590 010, Karnataka, India.
authors.forename: Preeti S
authors.initials: PS
authors.lastname: Salve
authors.affiliation: Department of Pharmaceutical Chemistry, KLE University's College of Pharmacy, Nehrunagar, Belagavi 590 010, Karnataka, India. Electronic address: sgalegaon@klepharm.edu.
authors.forename: Shankar G
authors.initials: SG
authors.lastname: Alegaon
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Hyderabad Campus, Secunderabad, Telangana State 500078, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
mesh_terms: D000634:Aminoquinolines / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000995:Antitubercular Agents / Q000737:chemistry* / Q000494:pharmacology*; D027081:DNA Gyrase / Q000378:metabolism; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000201:enzymology; D012545:Schiff Bases / Q000737:chemistry / Q000494:pharmacology; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000737:chemistry* / Q000494:pharmacology*; D014376:Tuberculosis / Q000188:drug therapy; D014709:Vero Cells; D062367:ortho-Aminobenzoates / Q000737:chemistry* / Q000494:pharmacology*
chemical_list: D000634:Aminoquinolines; D000995:Antitubercular Agents; D012545:Schiff Bases; D059005:Topoisomerase II Inhibitors; D062367:ortho-Aminobenzoates; D027081:DNA Gyrase; C001920:4-aminoquinoline; C000219:anthranilamide
keywords: Anthranilamide Schiff bases; Antitubercular activity; DNA gyrase; Isatoic anhydride; Quinoline