World Journal of
Pharmaceutical and Life Sciences

LC–MS–SUPPORTED STRUCTURAL ELUCIDATION AND THERAPEUTIC IMPACT OF ISONIAZID–NAD ADDUCT 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 evaluates the in vitro antibacterial potency and cytotoxic profile of the Isoniazid-NAD adduct in Mycobacterium tuberculosis (H37Rv)–infected macrophage models (THP-1, RAW264.7), compared with the parent drug Isoniazid (INH). A five-assay screening panel quantified both bacterial inhibition and host-cell effects. Bacterial viability, measured by Resazurin/Alamar Blue and Luciferase Bioluminescence, showed strong inhibition by the Isoniazid-NAD adduct (28% and 27% viability) comparable to INH (22% and 25%), confirming its retained antibacterial efficacy. However, cytotoxicity assays revealed markedly elevated host apoptosis (34%), caspase-3/7 activation (2.8-fold), and LDH release (31%), indicating substantial pro-apoptotic and necrotic stress compared to INH (10%, 1.2-fold, 9%). These results suggest that while the Isoniazid-NAD adduct maintains potent antimycobacterial activity, it exhibits poor host selectivity and heightened macrophage toxicity, likely due to excessive reactive intermediate formation or oxidative stress. Overall, its cytotoxic burden limits therapeutic viability despite promising bacterial inhibition.

[Full Text Article]   [Download Certificate]