Investigation of the Effects of 1,2,4-Triazole and Thiazole Ring-Containing Hybrid Molecules on Carbonic Anhydrase I and II

Abstract

Carbonic anhydrase (CA, EC 4.2.1.1) is an enzyme that catalyzes the reversible reaction of carbon dioxide to bicarbonate and a proton under physiological conditions. Pharmaceutical research has gained importance since the design of novel compounds that inhibit CA I-II isoenzymes has a promising approach for pharmacological intervention in many diseases. Triazole derivatives have attracted attention due to their chemotherapeutic, antifungal, antiviral, antibiotic, analgesic, and antifungal activities. Therefore, in this study, the effect of 1,2,4-triazole and thiazole ring-containing compounds on human carbonic anhydrase I (hCA I) and II (hCA II) isoenzymes were investigated in vitro. For this purpose, hCA I and hCA II isoenzymes were purified by Sepharose-4B affinity column chromatography. Estimation of inhibition mechanism and drug-likeness characteristics of compounds were also determined using molecular docking simulation. The inhibitory effects of ten compounds were investigated. Activity vs. concentration graphs were prepared for each compound and IC50 values or AC50 were calculated from these graphs. It was revealed that some of the compounds exhibited selective inhibition on carbonic anhydrase isoenzymes. The studied compounds are considered to be drug candidates. 1,2,4-triazole and thiazole ring-containing hybrid molecules inhibited hCA-I isoenzyme with IC50 values between 0.135 and 0.523 mM and hCA II with IC50 values between 0.108 and 0.523 mM. Molecule 8 showed the highest inhibition potency against hCA-I while molecule 3 showed the highest inhibitory effect against hCA-II. Estimated binding energies for molecule 10 into hCA I is -9.31 kcal/mol and for molecule 2 on hCA II is -8.21 kcal/mol. image