Design, synthesis and antitubercular assessment of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives

Rajubai D Bakale; Shubham M Sulakhe; Sanghratna L Kasare; Bhaurao P Sathe; Sanket S Rathod; Prafulla B Choudhari; Estharla Madhu Rekha; Dharmarajan Sriram; Kishan P Haval

doi:10.1016/j.bmcl.2023.129551

Design, synthesis and antitubercular assessment of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives

Bioorg Med Chem Lett. 2024 Jan 1:97:129551. doi: 10.1016/j.bmcl.2023.129551. Epub 2023 Nov 17.

Authors

Rajubai D Bakale¹, Shubham M Sulakhe¹, Sanghratna L Kasare¹, Bhaurao P Sathe¹, Sanket S Rathod², Prafulla B Choudhari², Estharla Madhu Rekha³, Dharmarajan Sriram³, Kishan P Haval⁴

Affiliations

¹ Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University SubCampus, Osmanabad 413501, MS, India.
² Department of Pharmaceutical Chemistry, Bharati Vidyapeeth College of Pharmacy, Kolhapur 416013, MS, India.
³ Department of Pharmacy, Birla Institute of Technology and Science-Pilani, Hyderabad Campus, Jawahar Nagar, Shameerpet Mandal, R. R. District, Hyderabad 500078, India.
⁴ Department of Chemistry, Dr. Babasaheb Ambedkar Marathwada University SubCampus, Osmanabad 413501, MS, India. Electronic address: havalkp@gmail.com.

PMID: 37979730
DOI: 10.1016/j.bmcl.2023.129551

Abstract

A library of 1, 2, 3-triazole incorporated thiazolylcarboxylate derivatives (7a-q) and (8a-j) were synthesized and evaluated for their in-vitro antitubercular activity against Mycobacterium tuberculosis H37Rv. The two compounds 7h and 8h have displayed excellent antitubercular activity with MIC values of 3.12 and 1.56 µg/mL respectively (MIC values of standard drugs; Ciprofloxacin 1.56 μg/mL & Ethambutol 3.12 μg/mL). Whereas, the four compounds 7i, 7n, 7p and 8i displayed noticeable antitubercular activity with a MIC value of 6.25 µg/mL. The active compounds of the series were further studied for their cytotoxicity against RAW264.7 cell line using MTT assay. Furthermore, to study the probable mechanism of antitubercular action, physicochemical property profiling, DFT calculation and molecular docking study were executed on mycobacterial cell wall target Decaprenylphosphoryl-β-d-ribose 2'-epimerase 1 (DprE1). Among all the compounds, 7h (-10 kcal/mol) and 8h (-10.1 kcal/mol) exerted the highest negative binding affinity against the targeted DprE1 (PDB: 4NCR) protein.

Keywords: 1,2,3-Triazoles; Antitubercular; Ethionamide; Molecular docking study; Prothionamide.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antitubercular Agents*
Microbial Sensitivity Tests
Molecular Docking Simulation
Mycobacterium tuberculosis*
Structure-Activity Relationship
Triazoles / chemistry

Substances

Antitubercular Agents
Triazoles