In silico screening of small molecules capable of inhibiting AT1 receptors for research and development of drugs to treat hypertension

Abstract

Inhibition of the AT1 receptor of angiotensin II is a common strategy in hypertension treatment. This study applied in silico screening methods to identify novel compounds with potential AT1 receptor inhibition. The structural data of compounds were collected from various chemical libraries. Molecular docking models and 3D-pharmacophore models were developed for screening purposes. Lipinski’s rule of five was employed to evaluate the drug-like potential of the compounds. The pharmacokinetic properties of potential compounds were analysed using the pkCSM tool. From an initial set of 21,994,845 compounds, 7,290 compounds satisfied the 3D-pharmacophore model, 7,103 compounds were successfully docked, and 626 compounds demonstrated higher affinity for the AT1 receptor than olmesartan. Among them, 10 compounds were identified as potential candidates due to their strong interactions with key amino acids and higher docking scores than olmesartan. All of these compounds comply with Lipinski's rule of five and exhibit favourable pharmacokinetic properties, making them suitable for oral drug formulation.