Structure based drug modeling: morinda citrifolia L. in breast cancer treatment / Nor Ayuni Zulkefly

Incidence of breast cancer is gradually increasing worldwide, therefore more effective anti-cancer drugs needed to treat this cancer. Focusing on discovering potential inhibitors against cancer-related proteins such as Epidermal Growth Factor Receptors (EGFR) tyrosine kinase that play critical roles in the development of the tumors can be helpful. EGFR tyrosine kinase inhibition by small molecules has been proved effective for cancer treatment. Lapatinib, the existing tyrosine kinase inhibitor has been widely used as chemotherapeutic drug for breast cancer treatment. By using knowledge on structure-based molecular modeling, identifying a new novel tyrosine kinase inhibitors in short timeframe with low cost become more rationale. Several compounds from Marinda citrifolia L. (Noni) with possible anti-cancer effects were identified and docking in silica approach was carried out. The binding affinity of ligand-protein complex was assessed by energy docking binding, inhibition constant and hydrogen bonding interactions. Amongst the molecular compounds, beta-sitosterol was discovered to have the lowest binding energy and inhibition constant value. Beta-sitosterol also has higher binding affinity than the existing drug, Lapatinib. By this finding, beta-sitosterol might have anti-cancer effects as potent as Lapatinib, thus can lead to the new development of tyrosine kinase inhibitors for breast cancer treatment.