Synthesis of new 2-(thiazol-4-yl)thiazolidin-4-one derivatives as potential anti-mycobacterial agents

• Published in: Bioorganic chemistry 2021-10, Vol.115, p.105192-105192, Article 105192
• Main Authors: Abhale, Yogita K., Shinde, Abhijit, Shelke, Monika, Nawale, Laxman, Sarkar, Dhiman, Mhaske, Pravin C.
• Format: Article
• Language: English
• Subjects: Animals; Antitubercular Agents - chemical synthesis; Antitubercular Agents - chemistry; Antitubercular Agents - pharmacology; Cell Line; Cytotoxicity; Humans; Microbial Sensitivity Tests; Mycobacterium bovis - drug effects; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Structure-Activity Relationship; Thiazole; Thiazoles - chemical synthesis; Thiazoles - chemistry; Thiazoles - pharmacology; Thiazolidin-4-one; Tuberculosis - drug therapy; Tuberculosis - veterinary
• ISSN: 0045-2068; 1090-2120
• DOI: 10.1016/j.bioorg.2021.105192

[Display omitted] •A series of 2-(thiazol-4-yl)thiazolidin-4-one derivatives (5a-t) were synthesized and evaluted for antimycobacterial activity.•Nine derivatives 5c, 5g, 5j, 5m, 5n, 5o, 5p, 5s, and 5 t showed excellent activity against M. bovis BCG with MIC 1.64–13.86 µg/mL (4.43–29.61 µM).•The substituents like Cl, F and CH3 on either one or both phenyl rings showed activity.•The active compounds were screened for cytotoxicity and found no cytotoxic activity. To search for potent antimycobacterial lead compounds, a new series of 3-substituted phenyl-2-(2-(substituted phenyl)thiazol-4-yl) thiazolidin-4-one (5a-t) derivatives have been synthesized by the condensation of 2-substituted phenyl thiazole-4-carbaldehyde with aromatic amine followed by cyclocondensation with thioglycolic acid. The structure of the newly synthesized 2-(thiazol-4-yl)thiazolidin-4-one derivatives were characterized by the spectroscopic analysis. The synthesized compounds were screened for antimycobacterial activity against Mycobacterium tuberculosis H37Ra (MTB) (ATCC 25177) and Mycobacterium bovis BCG (BCG, ATCC 35743). Most of the 2-(thiazol-4-yl)thiazolidin-4-one derivatives showed good to excellent antimycobacterial activity against both the Mtb strains. Nine derivatives 5c, 5g, 5j, 5m, 5n, 5o, 5p, 5s, and 5t showed excellent activity against M. bovis BCG with MIC 4.43 to 24.04 μM were further evaluated for the cytotoxicity activity against HeLa A549, and HCT-116 cell lines and showed no significant cytotoxic activity at the maximum concentration evaluated. The potential antimycobacterial activities enforced that the thiazolyl-thiazolidin-4-one derivatives could lead to compounds that could treat tuberculosis.