Caulerpenyne Compounds from Macroalgae Caulerpa sertularioides against MDM2 p53 Protein as an Anticancer Target

Abstract

Cancer remains a major global health burden, and limitations of current anticancer therapies highlight the need for safer and more effective alternatives. The MDM2–p53 interaction plays a crucial role in tumor progression by negatively regulating p53 tumor suppressor activity, making it an attractive molecular target for anticancer drug development. Marine macroalgae are recognized as promising sources of bioactive secondary metabolites with potential anticancer properties. This study aimed to investigate the potential of caulerpenyne, a sesquiterpenoid compound derived from the macroalgae Caulerpa sertularioides, as an inhibitor of the MDM2–p53 protein complex using an in silico molecular docking approach.

Molecular docking was performed using AutoDock Vina, with validation conducted through redocking of the native ligand, yielding an RMSD value of 0.69 Å, indicating a reliable docking protocol. Drug-likeness and pharmacokinetic properties were evaluated using SwissADME, showing that caulerpenyne fulfills Lipinski’s rule of five with favorable ADME characteristics. Docking results demonstrated that caulerpenyne binds to the MDM2–p53 receptor with a binding free energy of −6.2 kcal/mol and an inhibition constant of 28.5 µM. Interaction analysis revealed hydrogen bonding, hydrophobic, and π-interactions with key amino acid residues involved in p53 binding, including HIS75 and TYR79.

Although its binding affinity is lower than that of established synthetic inhibitors, caulerpenyne exhibits a comparable interaction pattern with critical residues of the MDM2 binding pocket. These findings suggest that caulerpenyne has potential as a natural lead compound targeting the MDM2–p53 pathway. Further experimental validation through in vitro and in vivo studies is required to confirm its biological efficacy and therapeutic potential.