Thrombin protease-activated receptor inhibitors from the peel of Ananas comosus (L.) Merr.: an in silico approach

[摘要] Background: Mortality and morbidity related to coronary atherothrombotic diseases and the unpredictable adverse effect of available anticoagulant drugs prompt the need for the development of effective and safe therapeutic agents. This study assessed the metabolomic profiling and molecular docking studies of the constituents of the unripe peel fruit of Ananas comosus (L.) Merr. methanolic extract against thrombin protease-activated receptors (PARs). Methods: Metabolomics profiling of the methanolic extract of the unripe peel of A. comosus was carried out using gas chromatography connected with a mass spectrometer (GC/MS). Molecular docking was done to assess the affinity of the identified compounds for the active sites of PARs, and the binding behaviors were visualized with DS BIOVIA. pkCSM, a web server, screened two probable compounds which presented ideal binding with all the receptors. Results: The GC/MS profiling showed a total of 12 volatile compounds with benzyl alcohol being the most prominent compound. The molecular docking analysis showed 2-(4-methylphenyl)-indolizine, and 2-p-nitrobenzoyl-1,3,5-tribenzyl- α-D-ribose demonstrated optimal binding with the selected PARs. The computed pharmacokinetic and pharmacodynamics properties of the selected compounds presented 2-(4-methylphenyl)-indolizine possesses drug-like properties. Conclusion: The findings of this study could be explored and optimized in the development of safe and efficient plant-based anti-thrombotic agents.

[学科分类] 生物科学（综合）

[关键词] A;comosus;Thrombin;Molecular docking;Protease-Activated Receptors