Network pharmacology-integrated molecular modeling analysis of Aquilaria malaccensis L. (agarwood) essential oil phytocompounds.

A network pharmacology approach was used to construct comprehensive pharmacological networks, elucidating the interactions between agarwood compounds and key biological targets associated with cancer pathways. We have employed a combination of network pharmacology, molecular docking and molecular dynamics to unravel agarwood plants' active components and potential mechanisms. Reported 23 molecules were collected from the agarwood plants and considered to identify molecular targets. Further, we identified ten potent targets related to cancer through network pharmacology analysis. The key targets include EGFR, JUN, TP53, SRC, MAPK3, ACTB, GAPDH, AKT1, MYC and CTNNB1. The biological processes include the negative regulation of fibroblast proliferation, metabolic, oxidative, and more. Subsequently, molecular docking results have indicated that 7-isopropenyl-1, 4a-dimethyl-4, 4a, 5,6,7,8-hexahydro-3 H-naphthalen-2-one showed an excellent binding affinity for all ten targets. This is the first study; we employed a novel integrated approach that combines network pharmacology, molecular docking and molecular dynamics simulation (MDS). The GO and KEGG, pathway enrichment analyses, shed light on biological processes relevant to cancer treatment. Moreover, molecular docking studies results indicated that the molecule 7-isopropenyl-1,4a-dimethyl-4,4a,5,6,7,8-hexahydro-3H-naphthalen-2-one exhibited strong binding affinity among all ten cancer targets, with a docking score ranging from - 9.9 to - 6.7 kcal/mol and found to have hydrogen bond interaction with Lys168, Ser322, Thr336 and Ala946 residues. MDS sheds light on the stability of their binding, the longevity of their interactions, and their overall effect on the enzyme's active site throughout the simulation. The current work signifies the initial report using bioinformatics approaches to assess the anticancer properties of compounds derived from the agarwood plant.