HPLC Profiling, Bioactive Characterization, in Vitro Cytotoxicity Evaluation, and Molecular Docking Study of Gallic Acid and Catechin from Leaves Extract of Cerbera odollam Geartn.

Abstract: Globally, the second most common cause of mortality is Cancer. This study aimed to explore the main phytoconstituents of Cerbera odollam Geartn leaves methanol extract and to estimate gallic acid and catechin cytotoxicity potential. cytotoxicity study was evaluated against nine cell lines; leukemia, non-small cell lung, colon, CNS, melanoma, ovarian, renal, prostate and breast cancer cells to ensure the efficacy of the biologically active components. The total phenolics and flavonoids concentrations were determined using RP-HPLC analysis. Cytotoxicity of (catechin and gallic acid) was accomplished by in-vitro single dose screening. HPLC analysis revealed the presence of 14 compounds, with high content of catechin and gallic acid as major compounds; which exhibiting cytotoxic properties. The screening results showed that gallic acid has moderate inhibitory activity against cell lines for non-small cell lung cancer (NCI-H226), colon cancer (KM12), and kidney cancer (UO-31) with ratio of 26.4%, 19% and 20.3%, growth inhibition percent; respectively. While catechin recorded growth inhibition activity against the NCI-H226 cell line and SNB-75 (CNS cancer) was moderate to modest by ratio 16% & 10.1%, respectively. The polyphenolic constituents have bioactive properties for improvement of the in vitro cytotoxic activity. Molecular docking analysis revealed that the investigated natural polyphenols bind stably within the EGFR T790M mutant active site through conserved hydrogen-bonding and favorable deep hydrophobic interactions involving key residues, including Leu718, Met790, Met793, and Leu844. Docking validation followed by molecular dynamics simulation refinement confirmed the reliability of the predicted binding modes and their potential relevance for EGFR-targeted inhibition.