Copyright (c) 2025 Niranjan Kaushik, SATENDRA KUMAR
This work is licensed under a Creative Commons Attribution 4.0 International License.
Design, Synthesis and Evaluation of Novel Quinoline-Thiazolidinone-Isonicotinamide Hybrids as Potent InhA Inhibitors for Antitubercular Therapy
Corresponding Author(s) : Niranjan Kaushik
Asian Journal of Chemistry,
Vol. 37 No. 12 (2025): Vol 37 Issue 12, 2025
Abstract
A series of quinoline–thiazolidinone–isonicotinamide hybrids (SK-1 to SK-12) was design, synthesized and characterized for their potential as antitubercular agent. The hybrid compounds were synthesized through a cyclization reaction using thioglycolic acid, affording yields of 63-76% with high stereoselectivity and their structure were confirmed by IR, 1H, 13C NMR, MS and elemental analysis. Molecular docking studies against M. tuberculosis Enoyl-ACP Reductase (InhA) revealed high binding affinities (-9.3 to -7.5 kcal/mol) significantly better than that of isoniazid (-7.5 kcal/mol) primarily mediated by hydrogen bonds with active-site residues such as ASP54, PHE149 and TYR158. ADMET prediction indicated drug-likeness, effective gastrointestinal absorption, low blood–brain barrier permeability and reduced risk of mutagenicity and carcinogenicity. In vitro antitubercular assay was performed by Microplate Alamar Blue Assay (MABA) and Low Oxygen Recovery Assay (LORA) methods, results showed that derivatives SK-3, SK-5 and SK-6 exhibited significant antitubercular activity as compared to isoniazid.
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S. Dhingra, N.A.A. Rahman, E. Peile, M. Rahman, M. Sartelli, M.A. Hassali, T. Islam, S. Islam and M. Haque, Front. Public Health, 8, 535668 (2020); https://doi.org/10.3389/fpubh.2020.535668
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Y.V.D. Nageswar, K. Ramesh and K. Rakhi, Curr. Green Chem., 12, 234 (2025); https://doi.org/10.2174/0122133461335061241101114827
S. Nirwan, V. Chahal and R. Kakkar, J. Heterocycl. Chem., 56, 1239 (2019); https://doi.org/10.1002/jhet.3514
S.K. Bera, M. Irfan and A. Porcheddu, ChemCatChem, 17, e202401813 (2025); https://doi.org/10.1002/cctc.202401813
M.S. Tople, N.B. Patel and P.P. Patel, J. Iran. Chem. Soc., 20, 1 (2023); https://doi.org/10.1007/s13738-022-02648-y
L. Mohammadkhani and M.M. Heravi, Front. Chem., 8, 580086 (2020); https://doi.org/10.3389/fchem.2020.580086
S.G. Alegaon, V. U, K.R. Alagawadi, D. Kumar, R.S. Kavalapure, S.D. Ranade, S. Priya A and S.S. Jalalpure, J. Biomol. Struct. Dyn., 40, 6211 (2022); https://doi.org/10.1080/07391102.2021.1880479
P. Seboletswe, N. Cele and P. Singh, ChemMedChem, 18, e202200618 (2023); https://doi.org/10.1002/cmdc.202200618
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