World Journal of
Pharmaceutical and Life Sciences

LC–MS–GUIDED ANALYTICAL EVALUATION AND CYTOTOXIC CORRELATION OF ACETYLISONIAZID 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 properties of Acetylisoniazid, a metabolic derivative of Isoniazid (INH), in macrophage infection models using Mycobacterium tuberculosis (H37Rv). A five-assay panel was conducted to evaluate antibacterial efficacy and host-cell safety. Bacterial viability was assessed using the Resazurin Microtiter Assay (REMA/Alamar Blue) and Luciferase Bioluminescence, while host cytotoxicity was determined via Annexin V/PI staining, Caspase-3/7 activity, and LDH release assays. Acetylisoniazid reduced bacterial viability to 41% and luminescence to 39%, showing moderate antimycobacterial activity compared with INH (22% and 25%, respectively). However, cytotoxicity was significantly higher, with 26% apoptotic cells, a 2.2-fold caspase activation, and 24% LDH release, indicating substantial host-cell damage. These results suggest that Acetylisoniazid possesses partial antibacterial efficacy but poor host selectivity, likely due to increased reactivity or inefficient bacterial activation. Overall, its elevated cytotoxic potential limits its suitability as a standalone therapeutic analog, though it provides valuable mechanistic insight into INH metabolism and toxicity.

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