Facile benzothiazole-triazole based thiazole derivatives as novel thymidine phosphorylase and α-glucosidase inhibitors: Experimental and computational approaches

Abstract

The present study reports the new thiazole (A-L) derivatives based on benzothiazole fused triazole which were synthesized and assessed against thymidine phosphorylase and α-glucosidase enzymes. Several compounds with the same basic structure but different substituents were found to have high activity against the targeted enzymes, while others with the same basic skeleton but different substituents were found to have medium to low activity among the members of tested series. These analogs showed a varied range of inhibition in both case thymidine phosphorylase and alpha glucosidase, A (IC₅₀ = 7.20 ± 0.30 µM and IC₅₀ = 1.30 ± 0.70 µM), B (IC₅₀ = 8.80 ± 0.10 µM and IC₅₀ = 2.10 ± 0.30 µM), C (IC₅₀ = 8.90 ± 0.40 µM and IC₅₀ = 3.20 ± 0.20 µM) and thiazole containing analogs such as G (IC₅₀ = 11.10 ± 0.20 µM and IC₅₀ = 7.80 ± 0.20 µM) and H (IC₅₀ = 12.30 ± 0.30 µM and IC₅₀ = 6.30 ± 0.20 µM). When compared with standard drugs 7-Deazaxanthine, 7DX (IC₅₀ = 10.60 ± 0.50 µM) and acarbose (IC₅₀ = 4.30 ± 0.30 µM) respectively. These analogs were also subjected to molecular docking studies which indicated the binding interaction of molecules with active sites of the enzyme and strengthen the drug profile of these compounds. ADMET studies also predict the drug-like properties of these compounds, with no violations of drug likeness rules.