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Vol. 36 No. 12 (2024): Vol 36 Issue 12, 2024

Copyright (c) 2024 Dr. Sunita Shirke

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Novel Triazolo[4,3-a]pyrazines as Potential MmpL3 Inhibitors: Design, Synthesis, Antitubercular Evaluation and Molecular Docking Studies

https://doi.org/10.14233/ajchem.2024.32667
Jayashree Kshirsagar
Department of Chemistry, Vivekanand College, Kolhapur-416003, India; Department of Chemistry, The New College, Kolhapur-416012, India
https://orcid.org/0009-0002-9751-4341
Wilson Chandane
Department of Chemistry, Shivaji University, Kolhapur-416004, India
https://orcid.org/0000-0003-2073-8136
Dipak Hiwarale
Department of Chemistry, Vishwasrao Naik Arts, Commerce and Baba Naik Science Mahavidyalaya, Shirala-415408, India
https://orcid.org/0000-0001-9123-9962
Nitin Naik
Department of Microbiology, Shivaji University, Kolhapur-416004, India
https://orcid.org/0000-0002-2196-1527
Kailas Sonawane
Department of Microbiology, Shivaji University, Kolhapur-416004, India
https://orcid.org/0000-0003-0156-7466
Gajanan Rashinkar
Department of Chemistry, Shivaji University, Kolhapur-416004, India
https://orcid.org/0000-0002-7200-5260
Rajashri Salunkhe
Department of Chemistry, Shivaji University, Kolhapur-416004, India
Sunita Shirke
Department of Chemistry, Vivekanand College, Kolhapur-416003, India
https://orcid.org/0009-0007-7938-9723

Corresponding Author(s) : Sunita Shirke

sds.orgchem@gmail.com

Asian Journal of Chemistry, Vol. 36 No. 12 (2024): Vol 36 Issue 12, 2024

Abstract

A series of biologically active novel triazolo[4,3-a]pyrazines (5a-f) were synthesized and characterized by spectroscopic techniques. The synthesized compounds 5a-f were evaluated for their in vitro anti-tubercular (anti-TB) activity against drug-sensitive Mtb H37Rv (ATCC 27294) strain as well as two drug-resistant Mtb strains viz. Mtb H37Rv ATCC 35822 (INH-resistant) and Mtb H37Rv ATCC 35837 (ETH-resistant). The synthesized compounds 5a-f displayed good to moderate anti-TB activity against drug-sensitive, INH-resistant and ETH-resistant Mtb H37Rv strains. Among all the compounds tested, compound 5c was found to be significantly potent. It inhibited the growth of drug-sensitive, INH-resistant and ETH-resistant Mtb H37Rv strains with MIC values 0.59 ± 0.11 µM, 20.83 ± 0.67 µM and 15.37 ± 0.14 µM, respectively. Moreover, compounds 5a-f were also tested for their cytotoxic efficacy against the mammalian Vero cell line at a maximum concentration of 50 µM. Molecular docking experiments of compounds 5a-f with the mycobacterial membrane protein large 3 (MmpL3) were performed to justify the biological activity and provide insight into the possible mechanism of action and binding mode of compounds. In silico predictions were used to validate compound toxicity descriptors, drug scores and drug-likeness properties.

Keywords

Pyrazine Tuberculosis Cytotoxicity Molecular docking Drug-likeness
Kshirsagar, J., Chandane, W., Hiwarale, D., Naik, N., Sonawane, K., Rashinkar, G., … Shirke, S. (2024). Novel Triazolo[4,3-a]pyrazines as Potential MmpL3 Inhibitors: Design, Synthesis, Antitubercular Evaluation and Molecular Docking Studies. Asian Journal of Chemistry, 36(12), 2817–2826. https://doi.org/10.14233/ajchem.2024.32667
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