Work

Novel 2,4-thiazolidinedione-quinoline hybrid molecules as REV-ERBα modulators for the treatment of diabetes mellitus

Year: 2025

Type: article

Abstract: REV-ERBα, a nuclear receptor involved in circadian regulation of glucose and lipid metabolism, has emerged as a promising target for antidiabetic therapy. In this study, we report the design, synthesis, and dual-target biological evaluation of fifteen novel quinoline–thiazolidinedione (TZD) hybrids. These compounds were rationally designed using a pharmacophore hybridization approach to modulate REV-ERBα activity while simultaneously inhibiting key carbohydrate-metabolizing enzymes. Molecular docking studies were performed against the REV-ERBα ligand-binding domain (PDB: 8d8i), revealing favorable binding interactions for several analogs. To complement the nuclear receptor-focused analysis, all synthesized derivatives were assessed in vitro for their ability to inhibit α-amylase and α-glucosidase—enzymes directly involved in postprandial glucose regulation. Notably, the compounds exhibited significant enzyme inhibitory activity, with over 50% α-amylase inhibition across the series and concentration-dependent effects on α-glucosidase. This dual-target evaluation highlights the potential of these hybrid molecules as multifunctional antidiabetic agents, acting both through REV-ERBα modulation and enzymatic control of glycemic load.

Source: Journal of Molecular Structure

DOI: 10.1016/j.molstruc.2025.143716

Authors: Kiran Kumar Vunnam, K Durga Bhaskar Yamajala, Dhilli Rao Gorja, S N Murthy Boddapati, Naresh Kumar Katari

Institutions: GITAM University, Texila American University, University of KwaZulu-Natal

Language: English

Topic: Synthesis and biological activity

Subfield: Organic Chemistry

Field: Chemistry

Domain: Physical Sciences

SDG: Good health and well-being

Open Access status: hybrid

Estimated APC paid: $3,360