title: Synthesis and biological evaluation of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione as antimycobacterial agents.
abstract: Resistance among dormant mycobacteria leading to multidrug-resistant and extremely drug-resistant tuberculosis is one of the major threats. Hence, a series of 1,2,4-triazole-3-thione and 1,3,4-oxadiazole-2-thione derivatives (4a-5c) have been synthesized and screened for their antitubercular activity against Mycobacterium tuberculosis H37Ra (H37Ra). The triazolethiones 4b and 4v showed high antitubercular activity (both MIC and IC50) against the dormant H37Ra by in vitro and ex vivo. They were shown to have more specificity toward mycobacteria than other Gram-negative and Gram-positive pathogenic bacteria. The cytotoxicity was almost insignificant up to 100 μg/ml against THP-1, A549, and PANC-1 human cancer cell lines, and solubility was high in aqueous solution, indicating the potential of developing these compounds further as novel therapeutics against tuberculosis infection.
authors.affiliation: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune, India.
authors.forename: Amol D
authors.initials: AD
authors.lastname: Sonawane
authors.affiliation: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune, India.
authors.forename: Navnath D
authors.initials: ND
authors.lastname: Rode
authors.affiliation: Combi-Chem Resource Centre, CSIR-National Chemical Laboratory, Pune, India.
authors.forename: Laxman
authors.initials: L
authors.lastname: Nawale
authors.affiliation: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune, India.
authors.forename: Rohini R
authors.initials: RR
authors.lastname: Joshi
authors.affiliation: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune, India.
authors.forename: Ramesh A
authors.initials: RA
authors.lastname: Joshi
authors.affiliation: Division of Organic Chemistry, CSIR-National Chemical Laboratory, Pune, India.
authors.forename: Anjali P
authors.initials: AP
authors.lastname: Likhite
authors.affiliation: Combi-Chem Resource Centre, CSIR-National Chemical Laboratory, Pune, India.
authors.forename: Dhiman
authors.identifier: 0000-0002-3912-1104
authors.initials: D
authors.lastname: Sarkar
mesh_terms: D000995:Antitubercular Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D045744:Cell Line, Tumor; D006801:Humans; D008826:Microbial Sensitivity Tests; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000254:growth & development; D010069:Oxadiazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D013871:Thiones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D014230:Triazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014376:Tuberculosis / Q000188:drug therapy
chemical_list: D000995:Antitubercular Agents; D010069:Oxadiazoles; D013871:Thiones; D014230:Triazoles; C583463:1,3,4-oxadiazole; C045575:1,2,4-triazole
keywords: 1,2,4-triazole-3-thione; 1,3,4-oxadiazole-2-thione; antitubercular activity; cytotoxicity