| Abstract [eng] |
Potential drug derivatives were synthesized during the project by taking into account the physiological features of Mycobacterium pathogens. During the synthesis, thiadiazoles, thiourea-type compounds and Schiff bases containing a sulphanilamide moiety were obtained. To assess the bioavailability of all the resulting structures, in silico studies were performed to determine the therapeutic acceptability of the compounds using the „ADMETlab 2.0“ web tool, based on Lipinski‘s rule describing the possibility of derivatives consumption by enteral administration. Bioavailability was also assessed by determining possible intestinal absorption, P-glycoprotein affinity, cytochrome CYP3A4 inhibition, and blood-brain barrier permeability. Based on the results, it was identified that the minimum probability of enteral administration is typical for 4-[(2-{4-[(E)-(2-chloro-5-nitrobenzylidene)amino]-5-sulfanyl-4H-1,2,4-triazol-3-yl}ethyl)amino]benzenesulfonamide, which does not comply with the Lipinski‘s rule, but also, it was determined that the best gut absorption is achieved with thiadiazole-type derivatives. To elucidate the theoretical effects of synthesized derivatives on pathogens of the Mycobacterium, molecular modeling has been performed using „AutoDockTools 1.5.7“. The study assessed the affinity of all synthesized structures for the Mycobacterium tuberculosis H37Rv enzyme InhA, with N-(5-{2- [(4-sulfamoylphenyl)amino]ethyl}-1,3,4-thiadiazol-2-yl) benzamide having the highest affinity for the target. |
