title: Design, development of new synthetic methodology, and biological evaluation of substituted quinolines as new anti-tubercular leads.
abstract: Two series of quinoline-based compounds were designed, synthesised and evaluated for anti-tubercular activity against Mycobacterium tuberculosis H37Rv (ATCC 27294 strain). A new method for Friedländer quinoline synthesis has been developed in water under the catalytic influence of the Brønsted acid surfactant DBSA. Among the forty-two compounds tested for anti-TB activity, twenty-three compounds exhibited significant activity against the growth of M. tuberculosis (MIC 0.02-6.25μg/mL). In particular, the compounds 3b and 3c displayed excellent anti-TB activity with MIC values of 0.2 and 0.39μg/mL, respectively, and are more potent than the standard drugs E, Cfx and Z that are clinically used to treat TB. The cytotoxicity of the compounds with MIC ⩽6.25μg/mL was evaluated against Human Embryonic Kidney 293T cell lines and all of the active compounds were found to be nontoxic (<50% inhibition). The results suggest that the synthesised substituted quinolines are promising leads for development of new drug to treat TB.
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar 160 062, Punjab, India.
authors.forename: Babita
authors.initials: B
authors.lastname: Tanwar
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar 160 062, Punjab, India.
authors.forename: Asim
authors.initials: A
authors.lastname: Kumar
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Perumal
authors.initials: P
authors.lastname: Yogeeswari
authors.affiliation: Department of Pharmacy, Birla Institute of Technology & Science - Pilani, Hyderabad Campus, Jawahar Nagar, Hyderabad 500 078, India.
authors.forename: Dharmarajan
authors.initials: D
authors.lastname: Sriram
authors.affiliation: Department of Medicinal Chemistry, National Institute of Pharmaceutical Education and Research (NIPER), Sector 67, S. A. S. Nagar 160 062, Punjab, India. Electronic address: akchakraborti@niper.ac.in.
authors.forename: Asit K
authors.initials: AK
authors.lastname: Chakraborti
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D057809:HEK293 Cells; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D011804:Quinolines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D014376:Tuberculosis / Q000188:drug therapy* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents; D011804:Quinolines
keywords: Anti-mycobacterial agents; Catalyst; DBSA; New synthetic methodology; Structural activity relationship; Substituted quinolines; Water