World Journal of
Pharmaceutical and Life Sciences

LC–MS–DRIVEN QUANTIFICATION AND BIOTRANSFORMATION STUDY OF ISONIAZID PYRUVATE IN MYCOBACTERIUM TUBERCULOSIS–INFECTED CELL LINE MODELS

Ayesha Ayub Khan*, Dr. Syed Ahmed Hussain, Ghousia Begum, Nada Ahmed Al Amoodi, Fariya Sultana, Bilquis Begum, Somabatthini Shruthi, Muskan Khatoon

ABSTRACT

This study investigates the in vitro antibacterial and cytotoxic characteristics of Isoniazid Pyruvate, a structural analog of Isoniazid (INH), using M. tuberculosis–infected macrophage models (THP-1, RAW264.7) infected with the H37Rv strain. A five-assay panel evaluated bacterial inhibition and host-cell safety. Bacterial viability was assessed using the Resazurin Microtiter Assay (REMA/Alamar Blue) and Luciferase Bioluminescence, while host cytotoxicity was measured through Annexin V/PI staining, Caspase-3/7 activity, and LDH release. Isoniazid Pyruvate showed limited antimycobacterial efficacy, reducing bacterial viability to 82% and luminescence to 80%, compared to INH (22% and 25%, respectively). Cytotoxicity was moderate, with 16% apoptosis, 1.5-fold caspase activation, and 14% LDH release, indicating mild host-cell stress relative to control. These results suggest that Isoniazid Pyruvate displays poor antibacterial potency but acceptable cytocompatibility, likely due to reduced intracellular activation or structural modification hindering target engagement. Overall, it is less effective than INH yet offers insights into prodrug design for improved selectivity and reduced host toxicity.

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