Exploring Cadaba fruticosa bioactive compounds for oral cancer an in silico and in vitro approach

This study evaluates the efficacy of phytotherapy in treating oral cancer. This study evaluated the phytocompounds extracted from Cadaba fruticosa for anticancer potential using GC-MS analysis. A total of 10 bioactive phytocompounds were identified, of which 3,5-dichloro benzyl propyl ester emerged as a highly potent candidate. A pharmacokinetic analysis was performed using SwissADME, and the selected compound did not adhere to Lipinski's rule of five, indicating no toxicity. A network pharmacology and molecular docking study was conducted to investigate the interaction between these compounds and the target proteins of oral cancer. The Kyoto Encyclopedia of Genes and Genomes (KEGG) database provided 10 hub genes associated with critical pathways: EGFR, MAPK3, PPARG, MTOR, KRAS, MDM2, ERBB2, IRS1, HRAS, and JAK2. Molecular docking studies confirmed strong binding interactions between 3,5-dichlorobenzyl propyl ester and the oral cancer protein SMAD, which had binding energy of -7.9 kcal/mol and interactions with the amino acids TYR280 (2.89 Å), ARG285 (3.04 Å), THR413 (3.21 Å), ARG415 (2.98 Å) and SER276 (2.09 Å), TYR280 (3.74 Å), THR289 (4.09 Å), ARG285 (4.31 Å), ARG415 (3.63 Å), ARG410 (3.54 Å), HIS441 (5.07 Å), PRO360 (4.45 Å), ARG410 (4.46 Å), ARG410 (4.93 Å) and ALA278 (4.34 Å). A molecular dynamics simulation was performed over 200 ns and showed the complex stable, with RMSD values ranging from 0.2 to 0.8 nm. Apoptotic gene expression analysis of KB-1 oral cancer cell lines showed downregulation of Bcl-2 and upregulation of pro-apoptotic genes BAD, BAX, and caspase-3 at an IC₅₀ of 38.60 µg/ml. In a density functional theory (DFT) analysis, 3,5-dichloro benzyl propyl ester was found to have HOMO and LUMO energy levels ranging from - 0.8100 to 0.2701, highlighting its electronic properties. The RDG scattered plot topological analysis indicated significant Van der Waals interactions and steric repulsions. Accordingly, the present study concludes that 3,5-dichloro benzyl propyl ester is a promising new drug for treating oral cancer.