Pyridine appended 2-hydrazinylthiazole derivatives: design, synthesis, in vitro and in silico antimycobacterial studies. Issue 29 (22nd June 2022)

• Record Type: Journal Article
• Authors: Matsa, Ramkishore; Makam, Parameshwar; Sethi, Guneswar; Thottasseri, Ahammed Ameen; Kizhakkandiyil, Aswani Raj; Ramadas, Krishna; Mariappan, Vignesh; Pillai, Agieshkumar Balakrishna; Kannan, Tharanikkarasu
• Is Part Of: RSC advances. Volume 12:Issue 29(2022)
• Page Start: 18333
• Page End: 18346
• Publication Date: 2022-06-22
• Subjects: Chemistry -- Periodicals; 540.5
• DOI: 10.1039/d2ra02163c
• Languages: English
• ISSNs: 2046-2069

Abstract

Abstract : Thirty novel pyridine-appended 2-hydrazinylthiazole derivatives have been synthesized and tested for their antimycobacterial activity against Mictrobactrium tuberculosis, H37Rv strain. Abstract : An array of pyridine appended 2-hydrazinylthiazole derivatives has been synthesized to discover novel chemotherapeutic agents for Mycobacterium tuberculosis ( Mtb ). The drug-likeness of pyridine appended 2-hydrazinylthiazole derivatives was validated using the Lipinski and Veber rules. The designed thiazole molecules have been synthesized through Hantzsch thiazole methodologies. The in vitro antimycobacterial studies have been conducted using Luciferase reporter phage (LRP) assay. Out of thirty pyridine appended 2-hydrazinylthiazole derivatives, the compounds 2b, 3b, 5b, and 8b have exhibited good antimycobacterial activity against Mtb, an H37Rv strain with the minimum inhibitory concentration in the range of 6.40–7.14 μM. In addition, in vitro cytotoxicity of active molecules has been observed against Human Embryonic Kidney Cell lines (HEK293t) using MTT assay. The compounds 3b and 8b are nontoxic and their cell viability is 87% and 96.71% respectively. The in silico analyses of the pyridine appended 2-hydrazinylthiazole derivatives have been studied to find the mode of binding of the active compounds with KasA protein of Mtb . The active compounds showed a strong binding score (−5.27 to −6.23 kcal mol −1 ).