New Succinimide-Thiazolidinedione Hybrids As Multitarget Antidiabetic Agents: Design, Synthesis, Bioevaluation, and Molecular Modelling Studies

Overview

Journal Molecules

Publisher MDPI

Specialty Biology

Date 2023 Feb 11

PMID 36770873

Authors

Mohammed A Huneif

Mater H Mahnashi

Muhammad Saeed Jan

Muhammad Shah

Sultan A Almedhesh

Seham M Alqahtani

Mohammad Jamaan Alzahrani

Muhammad Ayaz

Farhat Ullah

Umer Rashid

Abdul Sadiq

Affiliations

Soon will be listed here.

Abstract

Diabetes mellitus (DM) is a metabolic disorder majorly arising from the pathophysiology of the pancreas manifested as a decline in the insulin production or the tissue's resistance to the insulin. In this research, we have rationally designed and synthesized new succinimide-thiazolidinedione hybrids for the management of DM. In a multistep reaction, we were able to synthesize five new derivatives (). All the compounds were new containing a different substitution pattern on the N-atom of the succinimide ring. Initially, all the compounds were tested against the in vitro α-glucosidase, α-amylase, PTP1B, and DPP4 targets. In all of these targets, the compound was observed to be the most potential antidiabetic agent. Based on this, the antidiabetic activity of the compound was further investigated in experimental animals, which overall gave us encouraging results. The molecular docking studies of the compound was also performed against the target enzymes α-glucosidase, α-amylase, PTP1B, and DPP4 using MOE. Overall, we observed that we have explored a new class of compounds as potential antidiabetic agents.

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