Antimycobacterially active salicylanilide diethyl phosphates were evaluated to identify their potential drug target(s) for the inhibition of several mycobacterial enzymes, including isocitrate lyase, L-alanine dehydrogenase (MtAlaDH), lysine ε-aminotransferase, chorismate mutase, and pantothenate synthetase. The enzymes are related to the nongrowing state of Mycobacterium tuberculosis. Salicylanilide diethyl phosphates represent new candidates with significant inhibitory activity especially against L-alanine dehydrogenase. The most active MtAlaDH inhibitor, 5-chloro-2-[(3-chlorophenyl)carbamoyl]phenyl diethyl phosphate, has an IC50 of 4.96 µM and the best docking results. Other mycobacterial enzymes were mostly inhibited by some derivatives but at higher concentrations; isocitrate lyase showed the highest resistance to salicylanilide diethyl phosphates.

Department of Biochemical Sciences Faculty of Pharmacy Charles University Prague Heyrovského 1203 500 05 Hradec Králové Czech Republic

Department of Inorganic and Organic Chemistry Faculty of Pharmacy Charles University Prague Heyrovského 1203 500 05 Hradec Králové Czech Republic

Medicinal Chemistry Research Laboratory Pharmacy Group Birla Institute of Technology and Science Hyderabad 500078 India

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