Synthesis of 1,2,4-triazole-5-on derivatives and determination of carbonic anhydrase II isoenzyme inhibition effects.

In this study, some 1,2,4-triazole derivatives were synthesized and CA II inhibition potentials of these molecules were examined. It has been found that molecule 7c was the most potent inhibitor with the lowest IC50 value at micromolar level among the examined molecules. The inhibition in the range of 18.41-64.97% was seen in the presence of newly synthesized molecules at their reachable maximum concentration in the reaction mixtures. Kinetic studies showed that the inhibition mechanism of compound 7c on carbonic anhydrase activity was reversible and uncompetitive. Molecular docking studies also indicated that compound 7c could bind to the active site of the enzyme by weakly interacting with especially Gln102, Leu240, Ala241 and Trp243. ADME properties of these newly synthesized (3a-e, 6, 7a-e) were also studied and showed good oral drug candidate like properties. PMID: 30380445 [PubMed - as supplied by publisher]
Source: Bioorganic Chemistry - Category: Chemistry Authors: Tags: Bioorg Chem Source Type: research