Design, synthesis, α-amylase and glucose diffusion inhibition, and molecular docking studies of new indenopyrazolones bearing benzothiazole derivatives

Abstract

An eco-friendly facile synthesis of a series of twenty 1-(4/6-substitutedbenzo[d]thiazol-2-yl)-3-(phenyl/substitutedphenyl)indeno[1,2-c]pyrazol-4(1H)-ones 7a–t was achieved by the reaction of 2-(benzoyl/substitutedbenzoyl)-(1H)-indene-1,3(2H)-dione 3a–t and 2-hydrazinyl-4/6-substitutedbenzo[d]thiazole 6a–t in presence of freshly dried ethanol and glacial acetic acid under reflux conditions in good yields. The newly synthesized derivatives were well characterized using different physical and spectral techniques (FTIR, 1H NMR &13C NMR, and HRMS). All the compounds were subjected to assess their in vitro α-amylase and glucose diffusion inhibitory activity. Amongst them, the compounds 7i and 7l showed better α-amylase inhibitory activity demonstrating IC50 values of 92.99±1.94 µg/mL and 95.41±3.92 µg/mL, respectively in comparison to the standard drug acarbose (IC50 value of 103.60±2.15 µg/mL). The derivatives 7d and 7k exhibited good glucose diffusion inhibition with values of 2.25±1.16 µg/mL and 2.63±1.45 µg/mL, respectively with standard reference acarbose (2.76±0.55 µg/mL). The observed α-amylase inhibitory activity findings were corroborated through molecular docking investigations, particularly for the highly active compounds 7i (binding energy −8.0 kcal/mol) and 7l (binding energy −8.2 kcal/mol) respectively, in comparison to acarbose with a value of binding energy −6.9 kcal/mol for α-amylase.