<i>In Silico</i> Study of the Anti-MYC Potential\nof Lanostane-Type Triterpenes

One of the most investigated molecular targets for anticancer\ntherapy\nis the proto-oncogene <i>MYC</i>, which is amplified and\nthus overexpressed in many types of cancer. Due to its structural\ncharacteristics, developing inhibitors for the target has proven to\nbe challenging. In this study, the anti-MYC potential of lanostane-type\ntriterpenes was investigated for the first time, using computational\napproaches that involved ensemble docking, prediction of structural\nproperties and pharmacokinetic parameters, molecular dynamics (MD),\nand binding energy calculation using the molecular mechanics-generalized\nborn surface area (MM-GBSA) method. The analysis of physicochemical\nproperties, druglikeness, and pharmacokinetic parameters showed that\nligands ganoderic acid E (<b>I</b>), ganoderlactone D (<b>II</b>), ganoderic acid Y (<b>III</b>), ganoderic acid Df\n(<b>IV</b>), lucidenic acid F (<b>V</b>), ganoderic acid\nXL<sub>4</sub> (<b>VI</b>), mariesiic acid A (<b>VII</b>), and phellinol E (<b>VIII</b>) presented properties within\nthe filter used. These eight ligands, in general, could interact with\nthe molecular target favorably, with interaction energy values between\n−8.3 and −8.6 kcal mol<sup>–1</sup>. In MD, the\nresults of RMSD, RMSF, radius of gyration, and hydrogen bonds of the\ncomplexes revealed that ligands <b>I</b>, <b>IV</b>, <b>VI</b>, and <b>VII</b> interacted satisfactorily with the\nprotein during the simulations and assisted in its conformational\nand energetic stabilization. The binding energy calculation using\nthe MM-GBSA method showed better results for the MYC-<b>VII</b> and MYC-<b>I</b> complexes (−44.98 and −41.96\nkcal mol<sup>–1</sup>, respectively). These results support\nthe hypothesis that such molecules can interact with MYC for a considerable\nperiod, which would be an essential condition for them to exert their\ninhibitory activity effectively.