In silico evaluation of garlic-derived organosulfur compounds as multi-target inhibitors of breast cancer biomarkers

Breast cancer is the leading cause of cancer mortality among women worldwide, with drug resistance complicating treatment. Garlic-derived organosulfur compounds have demonstrated anticancer potential, however, their multi-target activity against key breast cancer biomarkers is not fully understood. This study utilized AutoDock Vina for molecular docking, along with the SWISS-ADME and PreADMET platforms for ADMET profiling, to evaluate six garlic compounds (Z-ajoene, allyl-methyl trisulfide, diallyl disulfide, diallyl sulfide, diallyl trisulfide, and S-allyl-L-cysteine) against clinically relevant breast cancer targets (Bcl-2, XIAP-BIR2, CDK-2, CDK-6, topoisomerases I/II, VEGFR2, and G-quadruplex DNA). Z-ajoene strongly binds to Bcl-2, Topoisomerase II, and CDK-2, while S-allyl-L-cysteine inhibits five targets. All compounds adhered to Lipinski’s rule of five, suggesting good oral bioavailability, and exhibited favorable ADMET properties with no mutagenic or tumorigenic risks. However, P-glycoprotein and CYP2C9 inhibition indicate potential drug interactions. Despite moderate affinities, these compounds are promising multi-target agents in breast cancer therapy. This study provides a basis for future research into garlic-based anticancer agents to overcome drug resistance.