Molecular modeling for potential cathepsin L inhibitor identification as new anti-photoaging agents from tropical medicinal plants

Ultraviolet exposure can cause photoaging toward the human skin which is begun by the inflammation on the exposure area, also resulting in activation of a degradative enzyme cathepsin L. This enzyme is one of the interesting novel therapeutic targets for antiaging agents. Three plants, named Kleinhovia hospita, Aleurites moluccana, and Centella asiatica, are well-known in the tropical region as anti-inflammatory herbs. The aims of this study were to predict the antiaging activity of the 31 compounds from these plants via inhibition of cathepsin L. All compounds were minimized their energies and then used in molecular docking. After that, molecular dynamics (MD) simulation was employed for the 5 candidate ligands and the positive control; schinol. Interaction analysis results of the pre-MD and post-MD simulation structures were obtained. Furthermore, a toxicity test was performed using ADMET Predictor 7.1. Based on the molecular docking and the MD simulation results, kleinhospitine A, β-amyrin, and castiliferol exhibited lower binding free energy than schinol (−27.0925, −28.6813, −26.0037 kcal/mol) and also had interactions with the S´ region binding site. The toxicity test indicated that β-amyrin is the most potential candidate since it exhibited the lowest binding energy and the high safety level.