Anticancer potential of Dendrocnide meyeniana through phytochemical profiling, ADMET analysis, molecular docking, and in silico cytotoxicity evaluation

Phytochemicals are widely explored for cancer therapeutics due to their structural diversity and broad pharmacological activities. This study investigated the phytochemical composition and anticancer potential of Dendrocnide meyeniana using integrated in silico approaches. Gas chromatography-mass spectrometry (GC-MS) and ultra-high-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UHPLC-QTOF-MS) identified 78 compounds, confirming the plant’s rich chemical diversity. Four cancer-related targets- EGFR, p53, MMP7 and CDK8/Cyclin C were selected for molecular docking to identify potential inhibitors. Drug-likeness and ADMET profiling of nine bioactive candidates revealed Cryptotanshinone as the most promising compound, exhibiting favorable pharmacokinetic and safety properties. Molecular docking showed that Cryptotanshinone possessed strong binding affinities toward EGFR ( -8.8 kcal/mol), p53 (-8.7 kcal/mol), MMP7 (-8.7 kcal/mol), and CDK8/Cyclin C (-9.8 kcal/mol), comparable to or exceeding the reference drug Erlotinib (-9.0 kcal/mol for EGFR). Toxicity prediction indicated no hepatotoxic, mutagenic, or cytotoxic effects, though the compound showed potential carcinogenic activity possibly linked to pathway-specific interaction in cell-cycle regulation. Molecular dynamics simulation further validated the stability of the Cryptotanshinone–EGFR complex, exhibiting moderate RMSD values and limited structural fluctuations indicative of stable interactions. Collectively, these findings highlight Cryptotanshinone from D. meyeniana as a promising natural lead for anticancer drug development, characterized by strong binding affinity, favorable pharmacokinetics, and structural stability in silico. Further in vitro and in vivo studies are warranted to confirm its therapeutic efficacy and safety.