Abstract
Background: People of all nationalities and social classes are now affected by the growing issue of hypertension. Over time, there has been a consistent rise in the fatality rate. A range of therapeutic compounds, on the other hand, are often used to handle hypertension
Objective: The objectives of this study are first to design potential antihypertensive drugs based on the DHP scaffold, secondly, to analyse drug-likeness properties of the ligands and investigate their molecular mechanisms of binding to the model protein Cav1.2 and finally to synthesise the best ligand.
Materials and Methods: Due to the lack of 3D structures for human Cav1.2, the protein structure was modelled using a homology modelling approach. A protein-ligand complex's strength and binding interaction were investigated using molecular docking and molecular dynamics techniques. DFT-based electronic properties of the ligand were calculated using the M06-2X/ def2- TZVP level of theory. The SwissADME website was used to study the ADMET properties.
Results: In this study, a series of DHP compounds (19 compounds) were properly designed to act as calcium channel blockers. Among these compounds, compound 16 showed excellent binding scores (-11.6 kcal/mol). This compound was synthesised with good yield and characterised. To assess the structural features of the synthesised molecule quantum chemical calculations were performed.
Conclusion: Based on molecular docking, molecular dynamics simulations, and drug-likeness properties of compound 16 can be used as a potential calcium channel blocker.
