prothionamide

Prothionamide is a thioamide-derivative small molecule used primarily as a second-line agent in the treatment of multidrug-resistant tuberculosis (MDR-TB) and leprosy. It is structurally similar to ethionamide and clinically interchangeable with it. Prothionamide acts as a prodrug that requires activation by the mycobacterial enzyme EthA (a monooxygenase), after which it forms an adduct with NAD. This adduct inhibits enoyl-acyl carrier protein reductase (InhA), an essential enzyme in the type II fatty acid synthase system responsible for mycolic acid biosynthesis—a critical component of the mycobacterial cell wall[1][6][8]. By inhibiting InhA, prothionamide disrupts cell wall synthesis and exerts bactericidal or bacteriostatic effects depending on drug concentration and organism susceptibility[7]. It has been approved for use since the late 1950s and remains recommended by international guidelines as part of combination regimens for MDR-TB when more effective drugs cannot be used[2][5].

Brand names

Prothionamide

Other names

protionamide