Design and optimisation of novel benzimidazole hybrid structures capable of simultaneous Peroxisome Proliferator Activated Receptor γ (PPARγ) and Angiotensin Receptor (ATR) modulation

Abstract

Introduction: Metabolic syndrome (MetS) has serious clinical implications and is linked to an increased predisposition to diabetes mellitus and cardiovascular disease. Polypharmacy, prevalent in the current management of MetS, is often inadequate in disease management. Literature indicates that dual PPARγ/ATR modulators have potential in the management of MetS.

Aim: To use the binding interactions of the benzimidazole scaffold with both PPARγ and ATR receptors to model structures with simultaneous high affinity for both ligand binding pockets using virtual screening and de novo design approaches.