Estudo racional de triterpenos do tipo lanostano como potenciais inibidores da proteína MYC: avaliação in silico

Abstract

The MYC protein is one of the most investigated molecular targets for anticancer therapy. The structural characteristics of this intrinsically disordered protein have made inhibitor development a challenge. Lanostane-type triterpenes, such as pisosterol, are secondary metabolites constantly investigated for their anticancer activities. In this study, the anti-MYC potential of 821 lanostane-type triterpenes was investigated using ensemble docking, structural property prediction, pharmacokinetic parameters, molecular dynamics, and free energy calculation using the MM-GBSA method. As a result, the ligands (I-VIII) known as ganoderic acid E (I), ganoderlactone D (II), ganoderic acid Y (III), ganoderic acid Df (IV), lucidenic acid F (V), ganoderic acid XL4 (VI), mariessiic acid A (VII), and phellinol E (VIII) exhibited properties within the filters used. These eight ligands interacted with the molecular target, presenting interaction energies between -8.3 and -8.6 kcal.mol-1. In molecular dynamics, the RMSD, RMSF, radius of gyration, and hydrogen bonding plots revealed that ligands I, IV, VI, and VII interacted satisfactorily with the protein during the simulations, contributing to its conformational and energetic stabilization. The MYC-I and MYC-VII complexes presented free energies of -41.96 kcal.mol-1 and -44.98 kcal.mol-1, respectively. These results demonstrate that lanostane-type triterpenes were able to interact with MYC, forming stable complexes, suggesting that these molecules have the potential to inhibit the target