Computational Study of Garlic Compounds as Potential Anti-Cancer Agents for the Inhibition of CCR5 and CXCR4

Abstract Current cancer treatment methods are still inadequate due to the complexity of the cancer progression mechanism, which involves multiple genes, proteins, and signaling pathways. The discovery and validation of novel anticancer compounds remains challenging. Garlic has many medicinal properties that can combat various diseases. Organosulfur present in garlic has been shown to induce apoptosis in cancer cells; however, the underlying mechanism of action of non-organosulfur compounds from garlic in controlling cancer cells remains unclear. The present study aimed to analyze the efficacy of organosulfur and non-organosulfur compounds, including the flavonoid, terpenoid, and saponin groups, as inhibitors of C-C chemokine receptor type 5 (CCR5) and C-X-C chemokine receptor type 4 (CXCR4), which play significant roles in the progression of cancer. To determine the interactions between the active compounds of garlic and these receptors (CCR5 and CXCR4), molecular docking was performed using the PyRx v.0.8 software. Amino acid residues were analyzed and visualized using Biovia Discovery Studio and PyMol, respectively. Non-organosulfur compounds exhibited better results than the organosulfur compounds in binding affinity analysis. Tigogenin (from the saponin group) is considered to be a CCR5 inhibitor, while lupeol (from the terpenoid group) is considered to be a CXCR4 inhibitor. In conclusion, our results suggest that garlic compounds could be promising inhibitors of CCR5 and CXCR4, which are highly expressed in cancer. However, further research is needed to validate the in vitro and in vivo activities of garlic compounds for the inhibition of cancer progression. Keywords: Anticancer agents, CCR5, CXCR4, Garlic, Organosulfur compounds, Non-Organosulfur compounds]