Drug likeness Properties ADME/T Analysis and Thrombolytic Activity of Phenolic Compounds in Allium sativum peel Extract - In-silico Approach

Phytochemicals are significant in the drug development, Allium sativum perennial herb distributed in Tropical Asia, it was commonly called Garlic. Its peel had various medicinal properties such as Cytotoxicity, Anti bacterial and Anti-inflammatory. Hence peel was also exploded for thrombolytic effect. Current work was performed to identify different phytochemicals in Ethanolic garlic peel extract (Allium sativum) based on previous literature and to perform molecular docking with Protein tissue plasminogen activator (tPA) for their potential thrombolytic activity, to analyze their drug similarity and also ADME/T profiles. Literature from 2010 to 2023 was searched for reported phenolic phytochemicals of peel extract. Four compounds i.e Caffeic acid, P-Coumarin, Ferulic acid, Di-ferulic acid were selected, Study focused on the molecular interactions between four phytochemical compounds selected as ligands. Their 2D structures were downloaded from Pub Chem Database in SDF format and later converted to PDB format by Openbabel tool and Tissue plasminogen activator (tPA) which is involved in the coagulation cascade, was selected as Protein, it’s structure was downloaded from Protein data bank in PDB format. Docking was done using Argus lab version.4. The grid box size was set at 151, 151, and 151 Å (x, y, and z). Caffeic acid, P-coumarin, ferulic acid and diferulic acid docked within the binding pocket tPA with binding energies of −9.17757kcal/mol, − 8.69086 kcal/mol, −8.42909kcal/mol and − 8.97502 kcal/mol. Among all ligands, caffeic acid interacted with largest number (20) of residues within the target molecule. In contrast, P-coumarin interacted with (8) amino acid residues, ferulic acid with (20) amino acid residues and diferulic acid with (18) amino acid residues. Caffeic acid has a better point of contact with low binding energies. Later ADME/T analysis for all compounds was performed using SWISS ADME/T. Caffeic acid, P-coumarin, Ferulic acid, and Diferulic acid obeyed Lipinski’s rule of five, Furthermore, Caffeic acid showed good drug similarity Property and the ADME/T profiling predicted that it was safe can be consumed by humans. However, further in - vivo studies might be needed for confirmation of the thrombolytic activity of caffeic acid.