Synthesis, enzyme inhibition, and molecular docking studies of a novel chalcone series bearing benzothiazole scaffold

Abstract

This study reports the facile synthesis of a novel series of benzothiazole-chalcones, in addition to their inhibitory profile on important metabolic enzymes including human carbonic anhydrases (hCA-I, hCA-II) and paraoxonase (PON-1). The inhibition parameters, IC₅₀ (concentration for 50% inhibition) and Ki (dissociation constant) values, toward the title enzymes were determined for the studied compounds. As a result, IC₅₀ values of hydratase activity were in the range 4.15-5.47 and 2.56-4.58 μM for hCA-I and hCA-II, respectively. At the same time, IC₅₀ values of esterase activity were in the range 24.91-104.00 and 35.25-97.00 μM, while Ki values were in the range 14.43-59.66 and 26.65-73.34 μM for hCA-I and hCA-II, respectively. In addition, PON-1 enzyme inhibition results showed interesting inhibitory effects, with IC₅₀ values between 13.28 and 16.68 μM. Finally, a comprehensive approach was established for the synthesized compounds based on theoretical calculations, which have been done using B3LYP, PBE0 theories and SVP, TVZP, TVZPP basis sets, followed by docking studies by which the outputs proved the harmonically flows with the experimental results.

Keywords: benzothiazole; carbonic anhydrase; chalcone; molecular docking; paraoxonase.