Experimental and computational analysis of benzothiophene as a selective inhibitors of diabetes mellitus

Abstract

Diabetes mellitus results in chronic hyperglycemia, affecting more than one hundred million people over the world. To treat diabetes mellitus, novel benzothiophene-derived thiadiazole analogues (1-17) were synthesized to biological assess their potential as lead inhibitors of both diabetic enzymes (α-amylase and α-glucosidase). These compounds showed quite remarkable potency against both enzymes and emerged as anti-diabetic agents. As a reference for their biological assessment, acarbose (5.90 ± 0.30 μM, 6.50 ± 1.80 μM) were used and in comparison to it analogue 3 having IC₅₀ of 4.20 ± 0.50 μM, 4.90 ± 1.50 μM, 6 with IC₅₀ of 3.10 ± 1.20 μM, 4.10 ± 0.80 μM, 10 with IC₅₀ of 5.20 ± 1.20 μM, 6.10 ± 2.10 μM and 16 having IC₅₀ of 3.90 ± 2.20 μM, 4.10 ± 1.20 μM emerged as most active analogues among the synthesized derivatives. Versatile attached functionalities such as CF₃, F, OH and Cl bind with the target proteins in order to inhibit their normal activity or function. Binding potency (interactive properties) of the leading compounds was also revealed under molecular docking. ADME analysis further unveiled that the potent compounds exhibit drug properties. Moreover, reactivity of these analogues with leading potential was also explored via density functional theory (DFT), revealing their molecular electrostatic potential, electrophilic, nucleophilic, HOMO and LUMO sites.