title: Design, synthesis and biological evaluation of novel quinoline-based carboxylic hydrazides as anti-tubercular agents.
abstract: In this study, seventeen novel quinoline-based carboxylic hydrazides were designed as potential anti-tubercular agents using molecular hybridization approach and evaluated in-silico for drug-likeness behavior. The compounds were synthesized, purified, and characterized using spectral techniques (like FTIR, (1) H NMR, and Mass). The in-vitro anti-tubercular activity (against Mycobacterium tuberculosisH37Ra) and cytotoxicity against human lung fibroblast cells were studied. Among the tested hydrazides, four compounds (6h, 6j, 6l, and 6m) exhibited significant anti-tubercular activity with MIC values below 20 μg/mL. The two most potent compounds of the series, 6j and 6m exhibited MIC values 7.70 and 7.13 μg/mL, respectively, against M. tuberculosis with selectivity index >26. Structure-activity relationship studies were performed for the tested compounds in order to explore the effect of substitution pattern on the anti-tubercular activity of the synthesized compounds.
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Rajasthan, India.
authors.forename: Subhash
authors.initials: S
authors.lastname: Chander
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Rajasthan, India.
authors.forename: Penta
authors.initials: P
authors.lastname: Ashok
authors.affiliation: Laboratory of Microbiology, Parasitology and Hygiene (LMPH), S7, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Davie
authors.initials: D
authors.lastname: Cappoen
authors.affiliation: Laboratory of Microbiology, Parasitology and Hygiene (LMPH), S7, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Wilrijk, Belgium.
authors.forename: Paul
authors.initials: P
authors.lastname: Cos
authors.affiliation: Medicinal Chemistry Research Laboratory, Department of Pharmacy, Birla Institute of Technology & Science, Pilani, Rajasthan, India. murugesan@pilani.bits-pilani.ac.in.
authors.forename: Sankaranarayanan
authors.initials: S
authors.lastname: Murugesan
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015195:Drug Design; D005347:Fibroblasts / Q000187:drug effects; D006801:Humans; D008826:Microbial Sensitivity Tests; D015394:Molecular Structure; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D011804:Quinolines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000995:Antitubercular Agents; D011804:Quinolines
keywords: Mycobacterium tuberculosis; cytotoxicity; drug likeness; fibroblast; quinoline