Synthesis and Biological Activity for 1,3,4-Thiadiazole-2-Iminothiazolidin-4-Ones: Antidiabetic and Anti-Alzheimer Activity.

Abstract

A series of 2-iminothiazolidin-4-one-1,3,4-thiazole hybrids 7a-l are synthesized and screened for their inhibitory activities against responsible enzymes in type 2 diabetes mellitus (T2DM) and Alzheimer's diseases. Among the compounds with potential inhibitory activity, several 2-iminothiazolidin-4-ones exhibit the strongest inhibitory activity against the screened enzymes, including 7c (IC₅₀ = 6.12 ± 0.11 µM, for α-amylase), 7e (IC₅₀ = 6.78 ± 0.15 µM, for α-glucosidase), 7k (IC₅₀ = 1.82 ± 0.04 µM, for DPP-4), 7f (IC₅₀ = 2.21 ± 0.02 µM, for PTP1B), 7h (IC₅₀ = 0.06 ± 0.01 nM, for AChE), 7j (IC₅₀ = 0.03 ± 0.01 nM, for BChE, and IC₅₀ = 0.32 ± 0.01 nM, for MAO-A), and 7l (IC₅₀ = 0.02 ± 0.01 nM, for MAO-B). Compound 7j exhibits the strongest inhibitory activity for both BChE and MAO-A. Compounds with short-chain alkyl groups (2-4 carbon atoms) have the strongest inhibitory activity against the enzymes responsible in T2DM, with the exception of 7k (with 6-carbon atom chain), whereas the long-chain alkyl groups (with 5-7 carbon atom chains) have the strongest inhibitory activity against the enzymes responsible in Alzheimer's disease. These compounds also exhibit the high antiglycation and antioxidant activity in DPPH and ABTS^•+ scavenging assays. They are noncytotoxic for WI-38 cell line with IC₅₀ > 76 μM.