Thiophene-2 (TP2) is a targeted inhibitor of polyketide synthase 13 (Pks13), specifically designed to disrupt mycolic acid biosynthesis. By doing so, it effectively induces rapid cell death in mycobacteria. Thiophene-2 demonstrates notable anti-tuberculosis activity and exhibits a minimum inhibitory concentration (MIC) value of 1 μM against Mycobacterium tuberculosis.

Mycobacterium tuberculosis:1 μM (MIC)

In vitro, TP inhibits fatty acyl-AMP loading onto Pks13. Thiophene-2 (TP2; 0-125 μM) inhibits loading of wild-type Mycobacterium tuberculosis (Mtb) Pks13 (Pks13_WT) in a dose-dependent manner. Thiophene-2 also inhibits palmitic acid (FL C16) loading onto the TP-resistant F79S mutant protein[1]. Thiophene-2 has an IC50 versus monkey kidney Vero cells and human liver carcinoma HepG2 cells of 17.5 and 7.30 μM, respectively. Significant intracellular killing activity within BCG-infected J774A.1 macrophage cells is observed at Thiophene-2 concentrations of 12.8 μM[1].