Design, synthesis, biological evaluation and molecular docking study of thiadiazole-isatin hybrid analogues as potential anti-diabetic and anti-bacterial agents

Abstract

We have synthesized thiadiazole-isatin hybrid analogues (1–20), characterized through different spectroscopic techniques such as ¹HNMR, ¹³CNMR, HREI-MS, and evaluated against α-glucosidase and α-amylase enzymes. All analogues showed potent inhibitory potentials, having an IC₅₀ values ranged from 22.08 ± 0.09 to 54.03 ± 0.07 μM (against α-amylase) and 19.03 ± 0.04 to 50.03 ± 0.02 μM (α-glucosidase) when compared with the standard drug acarbose (IC₅₀ = 22.07 ± 0.02 μM for α-amylase and IC₅₀ = 18.01 ± 0.06 μM for α-glucosidase respectively). Among the series, analogues 13 (IC₅₀ = 19.03 ± 0.04 and 22.08 ± 0.09 μM), 12 (IC₅₀ = 21.03 ± 0.07 and 24.03 ± 0.07 μM), and 5 (IC₅₀ = 22.02 ± 0.03 and 26.02 ± 0.04 μM) were identified as the most active inhibitors. The structure–activity relationship was carried out, mainly associated with the nature, number, position, and electron-donating and electron-withdrawing effects of the substituent (s) on the phenyl ring. With the help of molecular docking, the binding interaction of the most active analogues within the active site of enzymes was confirmed. Almost twelve compounds were also screened for antibacterial potential, and few were found to be effective against Bacillus subtilis. All compounds were verified for cytotoxicity against the 3 T3 mouse fibroblast cell line and detected non-toxic.