Design and Synthesis of Isatin-Tagged Isoniazid Conjugates with Cogent Antituberculosis and Radical Quenching Competence: In-vitro and In-silico Evaluations.

Autor: Gavadia R; Department of Chemistry, M. D. University, Rohtak, Haryana, 124001, India., Rasgania J; Department of Chemistry, M. D. University, Rohtak, Haryana, 124001, India., Sahu N; Department of Chemistry, M. D. University, Rohtak, Haryana, 124001, India., Varma-Basil M; Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India., Chauhan V; Department of Microbiology, Vallabhbhai Patel Chest Institute, University of Delhi, Delhi, 110007, India.; Department of Microbiology, M. D. University, Rohtak, Haryana, 124001, India., Kumar S; Department of Microbiology, M. D. University, Rohtak, Haryana, 124001, India., Mor S; Department of Chemistry, Guru Jambheshwar University of Science and Technology, Hisar, Haryana, 125001, India., Singh D; Department of Chemistry, M. D. University, Rohtak, Haryana, 124001, India., Jakhar K; Department of Chemistry, M. D. University, Rohtak, Haryana, 124001, India.
Jazyk: angličtina
Zdroj: Chemistry & biodiversity [Chem Biodivers] 2024 Oct; Vol. 21 (10), pp. e202400765. Date of Electronic Publication: 2024 Sep 06.
DOI: 10.1002/cbdv.202400765
Abstrakt: In pursuit of potential chemotherapeutic alternates to combat severe tuberculosis infections, novel heterocyclic templates derived from clinically approved anti-TB drug isoniazid and isatin have been synthesized that demonstrate potent inhibitory action against Mycobacterium tuberculosis, and compound 4i with nitrophenyl motif exhibited the highest anti-TB efficacy with a MIC value of 2.54 μM/ml. Notably, the same nitro analog 4i shows the best antioxidant efficacy among all the synthesized compounds with an IC 50 value of 37.37 μg/ml, suggesting a synergistic influence of antioxidant proficiency on the anti-TB action. The titled compounds exhibit explicit binding affinity with the InhA receptor. The befitting biochemical reactivity and near-appropriate pharmacokinetic proficiency of the isoniazid conjugates is reflected in the density functional theory (DFT) studies and ADMET screening. The remarkable anti-TB action of the isoniazid cognates with marked radical quenching ability may serve as a base for developing multi-target medications to confront drug-resistant TB pathogens.
(© 2024 Wiley-VHCA AG, Zurich, Switzerland.)
Databáze: MEDLINE
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