Targeting EP3 receptor for laxative drug discovery: molecular docking and virtual screening of ricinoleic acid analogues

Abstract

<title>Abstract</title> <bold>Introduction:</bold> Castor oil has long been recognized for its laxative activity and used in traditional medicine for the treatment of constipation. This study aimed to deepen our understanding of how castor oil acts as a laxative using computational modeling and to identify potential candidates for future drug development. <bold>Materials and methods:</bold> An in-silico approach was conducted via computational tools to investigate the laxative mechanism of castor oil. Molecular docking of the main components of castor oil with the molecular target 6AK3 has been performed. Virtual screening of 100 molecules related to ricinoleic acid was carried out using the Python Dockstring package. Physicochemical, pharmacokinetic, and toxicological parameters of ricinoleic acid and the top 10 related molecules were predicted via the SwissADME and PkCSM websites. <bold>Results and Discussion:</bold> Molecular docking indicated that ricinoleic acid has a strong affinity for the selected molecular target. Other components of castor oil also showed significant scores, warranting further investigation. Virtual screening identified related molecules with higher affinities than ricinoleic acid. After predicting their physicochemical, pharmacokinetic, and toxicological profiles, four compounds emerged as lead candidates based on their favourable binding profiles and ADMET predictions as candidates for drug development. <bold>Conclusion:</bold> These findings underscore the potential of castor oil, especially ricinoleic acid, along with four other promising molecules for developing laxative medications.