Targeting colorectal cancer with active compounds from Dillenia indica L. using in silico studies

Colorectal cancer (CRC) remains a significant global health issue, and the overexpression of MAPK14 has been linked to its progression and chemoresistance. The elephant apple, Dillenia indica, has shown promise in traditional medicine, with extracts exhibiting cytotoxic effects against cancer cell lines. However, the specific compounds responsible for this activity and their mechanisms against MAPK14 have not been thoroughly investigated. The primary objective of this study was to employ an in-silico approach to identify potential active compounds from Dillenia indica that inhibit the MAPK14 enzyme. Compounds from Dillenia indica were screened for drug-likeness. Promising ligands were subjected to molecular docking and dynamics simulations to evaluate their binding and stability with the MAPK14 enzyme. Molecular docking suggested nutriacholic acid, formononetin 7-glucuronide and (+)-dihydroisorhamnetin as the best ligands with binding affinities of −9.5 to −8.5 kcal/mol. ADMET analysis predicted the prioritized compounds as nontoxic, and (+)-dihydroisorhamnetin had unique blood-brain barrier permeability. These results suggest (+)-dihydroisorhamnetin is a potential lead candidate for MAPK14 inhibition due to its stability. These findings in silico offer a theoretical rationale for the anticancer effects of D. indica, but further comprehensive in silico and in vitro enzymatic assays will be necessary to confirm inhibitory efficacy and safety profiles.