The present exploration is a molecular docking study of some 2,9,9-trimethyl-10-(2-phenylacetoxy)-icosahydropicene-2-carboxylate derivatives; namely, (1R,2R,4aR,6aR,6bR,8aR,10R,12aR,12bR,14aR,14bR)-methyl-1-hydroxy-2,9,9-trimethyl- 10- (2-phenylacetoxy)-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,14a,14b-icosahydropicene-2-carboxylate (1) and (1R,2R,4aR,6aR,6bS,8aR,10R,12S,12aR,12bS,14aR)-methyl-1,12-dihydroxy-2,9,9-trimethyl-10-(2-phenylacetoxy)-1,2,3,4,4a,5,6,6a,6b,7,8,8a,9,10,11,12,12a,12b,14a,14b-icosahydropicene-2-carboxylate (2) against the inflammatory mediator 5-LOX by utilizing the Glide module of Maestro 9.1 software. The ligand 1 displayed a very strong binding with 5-LOX, demonstrating Glide score of -10.32 Kcal/mol, owing to the formation of four hydrogen bonding through the carbonyl (=O), hydroxyl (-OH) and oxo (-O-) groups present in the pharmacophore with the amino acid residues; Ala672, Asn554, Leu607 and Gln363. The compound 2 expressed limited binding with receptor residues; Phe177 and Gln413 through the hydroxyl group present, showing a Glide score of -7.46 Kcal/mol. The molecular docking of the derivatives demonstrated specific binding with the target 5-LOX which may exhibit as anti-inflammatory activity. The study highlights the importance of specific groups and their position in the pharmacophore which enabled better interaction with the target residues. The stereochemistry also played an immense role in the binding with the inflammatory mediator. From both the structures of this pharmacophore, a conclusion may be drawn regarding the optimized structure which will strongly bind via hydrogen bonding. However, more studies and rational design are universally needed for the practical development of these therapeutic inhibitors. The study will revolutionize the importance of icosahydropicene-2-carboxylate based inhibitors in the treatment of inflammatory conditions.
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