Abstract
LC–MS–INTEGRATED ANALYTICAL AND THERAPEUTIC EVALUATION OF ETHIONAMIDE IN MYCOBACTERIUM TUBERCULOSIS–INFECTED CELL LINE MODELS
Maimuna Fatima*, Dr. Syed Ahmed Hussain, Ayesha Ayub Khan, Ghousia Begum, Nada Ahmed Al Amoodi, Fariya Sultana, Bilquis Begum, Somabatthini Shruthi, Muskan Khatoon
ABSTRACT
This study investigates the in vitro antimicrobial and cytotoxic profiles of Ethionamide in macrophage-based Mycobacterium tuberculosis (M. tuberculosis H37Rv) infection models compared to the first-line drug Isoniazid (INH). A five-assay screening panel was employed, including two bacterial viability assays (REMA/Alamar Blue and luciferase bioluminescence) and three host-cell cytotoxicity assays (Annexin V/PI, Caspase-3/7 activity, and LDH release). Ethionamide showed negligible inhibition of bacterial growth, maintaining 100% bacterial viability and luminescence, whereas INH markedly reduced viability to 22% and 25%, respectively, confirming its potent bactericidal activity. Host-cell cytotoxicity remained minimal for both compounds, with apoptotic cell percentages (8% vs 10%) and LDH release (7% vs 9%) showing low toxicity profiles. Caspase-3/7 activation was minimal (<1.2-fold), indicating negligible apoptosis induction. Collectively, the results reveal that Ethionamide, under these conditions, exhibits limited anti-mycobacterial activity but excellent host-cell tolerance. This data provides a quantitative framework for evaluating drug potency and cytotoxic safety in macrophage infection models.
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