In Silico Investigation of Cymbopogon citratus Phytochemicals as Novel Therapeutic Candidates Against Colon Cancer

Colon cancer is a significant health concern in the world and efforts need to be made concerning formulating safer and effective therapeutic agents. Natural phytochemicals have been presented as a potential candidate because of their wide range of biological activities, and because of their good safety profile. The integrated insilico methodology was utilized in the current study in an attempt to determine the therapeutic potentiality of phytochemicals in Cymbopogon citratus against two major proteins of the colon cancer progression, cyclooxygenase-1 (COX-1) and cytochrome P450 17A1 (CYP17A1). Molecular docking, pharmacokinetic analysis and molecular dynamics (MD) simulations were employed to screen 32 phytochemicals. Docking revealed that both targets had strong binding interactions with a number of compounds, and ADMET profiling indicated that 1,8-cineole has good pharmacokinetic characteristics, such as potential to be absorbed well, balanced lipophilicity and low predicted toxicity. Interaction analysis revealed that, 1, 8 cineole develops stable complexes with COX-1 and CYP17A1 by hydrogen bonding and hydrophobic interactions. In addition to that, the 100ns MD simulations were used to verify structural stability of the protein-ligand complexes as indicated by the stable level of RMSD, decreased residue motion, preserved compactness, and well-behaved conformational dynamics. The thermodynamic stability of the complexes was also supported by principal component analysis and free energy landscape. All these results indicate that 1,8-cineole is a good dual-target inhibitor that has good pharmacological and chemical properties. This paper has a powerful computational basis upon which additional experimental research can be done and demonstrates the possibilities of Cymbopogon citratus phytochemicals in the creation of new therapeutic approaches to colon cancer treatment.