QSAR study on 4-alkynyldihydrocinnamic acid analogs as free fatty acid receptor 1 agonists and antidiabetic agents: Rationales to improve activity

Abstract

The free fatty acid receptor 1 (FFAR1) is a class A G-protein coupled receptor and a validated target to develop antidiabetic drugs. The present work describes the quantitative structure–activity relationship (QSAR) study of a series of 4-alkynyldihydrocinnamic acid analogs to rationalize their FFAR1 agonist activity. The various physicochemical and structural descriptors were derived from Molecular Operating Environment (MOE, 2011). The variable selection and model development were carried out using Combinatorial Protocol in Multiple Linear Regressions (CP-MLR) approach. The identified QSAR models highlighted the significance of solvent accessible surface area and associated hydrophobicity to the biological activity. The chemical features to improve hydrophobicity of 4-alkynyldihydrocinnamic acid analogs have been discussed. Keywords: Free fatty acid receptor 1, GPR40, QSAR, CP-MLR, Physicochemical property