**4.5 Tolcapone, Entacapone (catechol-O-methyltransferase (COMT) inhibitor)**

Entacapone and tolcapone are two catechol-O-methyltransferase inhibitors used as an adjunct in the treatment of Parkinson's disease. Both have shown some activity against *M. tuberculosis* with a relatively high minimum inhibitory concentration (MIC) of 260 μM observed for entacapone, which was significantly lower than the cytotoxic concentration [47]. Their proposed mechanism against TB is what makes these molecules an interesting class to investigate. The mechanism is similar to isoniazid; however, they do not need enzymatic activation to bind to the enoyl–acyl carrier protein reductase (InhA) target. Furthermore, it has been proposed that it might be a possible treatment in MDR-TB, as it could evade the KatG activation associated with isoniazid resistance in many resistant strains [19, 47].
