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.

• MeSH
• antituberkulotika chemie   MeSH
• bakteriální proteiny * antagonisté a inhibitory   chemie   MeSH
• inhibitory enzymů chemie   MeSH
• Mycobacterium tuberculosis enzymologie   MeSH
• salicylanilidy chemie   MeSH
• simulace molekulového dockingu * MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH