Computational studies on Morpho Butterfly Wings-based compounds as potential Human 3-alpha Hydroxysteroid Dehydrogenase type 3 inhibitors

Cancer continues to pose a significant health threat due to the rapid development of drug resistance. To tackle this issue, compounds derived from Morpho Butterfly Wings were assessed for their potential anti-cancer properties using computational methods. Quantum chemical optimization was conducted using density functional theory, and receptor interactions were evaluated through induced-fit docking and molecular dynamics simulations. The findings indicated that 3,8-dimethoxy-2,7-dihydrobenzo[1,2,3-cd:4,5,6-c'd']diindole-4,5,9,10-tetraone (compound 4) exhibited a heightened electron-donating ability due to its narrow HOMO–LUMO gap, while 3,8-dinitro-2,7-dihydrobenzo[1,2,3-cd:4,5,6-c'd']diindole-4,5,9,10-tetraone (compound 6) showed a strong electron-accepting characteristic with its minimal LUMO energy. Additionally, the docking studies identified compound 6 as the leading potential inhibitor, which led to its selection for molecular dynamics simulations; however, the subsequent binding free energy assessments, along with RMSD and RMSF evaluations, demonstrated that it possessed lower dynamic stability and a reduced binding affinity compared to the reference compound, Doxorubicin.