World Journal of
Pharmaceutical and Life Sciences

LC–MS–ASSISTED CHARACTERIZATION AND MECHANISTIC INVESTIGATION OF PROTHIONAMIDE IN MYCOBACTERIUM TUBERCULOSIS–INFECTED CELL LINE MODELS

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

ABSTRACT

This study evaluates the in vitro antitubercular and cytotoxic profiles of Prothionamide in comparison with Isoniazid (INH) using macrophage infection models (THP-1, RAW264.7) infected with Mycobacterium tuberculosis (H37Rv). A five-assay screening panel was designed—two assays measured bacterial viability (REMA/Alamar Blue and luciferase bioluminescence) and three assessed host-cell cytotoxicity (Annexin V/PI, Caspase-3/7 activity, and LDH release). Prothionamide exhibited moderate antibacterial activity, reducing bacterial viability to 74% and bioluminescence to 72%, while INH achieved potent inhibition (22% and 25%, respectively). Host-cell toxicity for Prothionamide remained low, with apoptosis (14%), Caspase-3/7 activation (1.4-fold), and LDH release (12%) comparable to INH. These findings demonstrate that Prothionamide possesses partial antimycobacterial efficacy and an excellent safety profile in host macrophages, highlighting its potential in multidrug-resistant tuberculosis regimens when combined with synergistic agents or improved delivery systems.

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