Identification and in silico evaluation of natural compounds from Annona muricata (soursop) leaves for colon cancer treatment

Annona muricata (soursop), a traditional medicinal plant renowned for its anticancer properties due to annonaceous acetogenins, was investigated to identify potent phytochemicals targeting colon cancer. Considering the significant role of genetic mutations such as MLH1 in colorectal carcinogenesis, this study aimed to explore natural compounds with therapeutic potential. Gas chromatography-mass spectrometry (GC-MS) analysis identified 52 phytochemicals from A. muricata, which were filtered through Lipinski's rule of five to select 14 drug-like candidates. Molecular docking using PyRx prioritized seven compounds-alpha-tocopherol, 4,6-O-benzylidene-D-galactose, methyl 3-(3,5-di-tert-butyl-4-hydroxyphenyl)propionate, (5 S)-2(3 H)-furanone dihydro-5-methyl-5-phenyl-, (2R,3R,4aR,5 S,8aS)-2-hydroxy-4a,5-dimethyl-3-(prop-1-en-2-yl)octahydronaphthalen-1(2 H)-one, naphthalene 1,2,3,4,5,6-hexahydro-4,7-dimethyl-1-(1-methylethyl)-, and isobutyl phenylacetate. Pharmacokinetic properties (ADMET) were evaluated, and electronic characteristics were analyzed via density functional theory (DFT). Molecular dynamics (MD) simulations over 100 ns confirmed the stability of drug-protein complexes through RMSD, radius of gyration (Rg), SASA, RMSF, and hydrogen bonding patterns. Results demonstrated that these phytochemicals exhibited superior binding affinities compared to standard therapy, 5-fluorouracil, with alpha-tocopherol notably outperforming it. ADMET analyses verified favorable pharmacokinetics, indicating non-toxicity and non-carcinogenicity. Stability assessments showed consistent parameters throughout the simulation. Overall, the prioritized phytochemicals from A. muricata, especially alpha-tocopherol, exhibit significant anticancer potential and stability, supporting further experimental validation and development as therapeutic agents for colon cancer.