Discovery of Novel Flavonoid Analogues as Angiotensin Converting Enzyme Inhibitors based on Pharmacophore Modelling and Virtual Screening Techniques

Abstract

New drugs for the inhibition of the angiotensin converting enzyme (ACE) are in development and they have to be screened before being considered for preclinical and clinical evaluation. The current study deals with the evaluation of ACE inhibitory activity of flavonoid compounds using in silico docking studies. In this perspective, 18 flavonoids derivatives were selected. The drug likeness, bioactivity score and toxicity profile of the flavonoid compounds were determined using softwares like molinspiration and PreADMET. Captopril, a known ACE inhibitor was used as the standard. All the flavonoid compounds were docked with ACE using the software AutoDock 4.2. Docking results showed that all the selected flavonoids showed binding energy ranging between -10.97 kcal/mol to -9.39 kcal/mol when compared with that of the standard -3.79 kcal/mol). Intermolecular energy -12.53 (FA8) kcal/mol to -11.2 (FA11) kcal/mol and the values for captopril was -4.98 kcal/mol. The exhibited inhibition constant by the flavonoid compound for the ACE was found with varying range of 9.07 nM (FA14) to 208.98 nm (FA11). All the selected compounds had lesser inhibition constant when compared to the standard captopril (-1.67 mM). FA14 contributed better ACE binding energy because of its structural parameters and it can be synthesized and evaluated for its in vitro and in vivo potential and can be used as an effective ACE inhibitor for the prevention and protection against cardiovascular diseases.