Investigação das propriedades reativas e do potencial antiparkinson através de cálculos DFT e docking molecular de alcaloides protoberberínicos de Guatteria friesiana

Abstract

The present work addresses the computational theoretical study of the protoberberine alkaloids 13-hydroxy-discretinine and 7,8-dihydro-8-hydroxypalmatine, previously isolated from the plant of Guatteria friesiana genus, employing the density functional theory (DFT) to analyze their electronic and pharmacological properties. Using the Gaussian 09 software, the frontier molecular orbitals HOMO and LUMO, global reactivity indices (hardness, chemical potential, electronegativity, and electrophilicity index), local reactivity indices (Fukui indices), as well as the electrostatic potential maps (ESP) and average local ionization energy (ALIE) using the Multiwfn program were obtained at the B3LYP-D3(BJ)/6-311++G(2df, 2pd) revealed that the alkaloids exhibit distinct reactivities, with nucleophilic and electrophilic sites located on rings A, D (13-hydroxy-discretinine) and rings B, C (7,8-dihydro-8-hydroxypalmatine). Solvation free energies calculated for both alkaloids using: water, acetone, dichloromethane, and metanol; it was revealed that they have higher solubility in dichloromethane. Finally, using the Autodock Vina software, molecular docking calculations with human serum albumin (HSA), responsible for drug transport in the bloodstream, as well as the monoamine oxidase A (MAO-A) and B (MAO-B) enzymes, target enzymes in the treatment of Parkinson's disease, were evaluated, indicating that the alkaloids preferentially inhibit MAO-B (-8.0 and 5.7 kcal/mol) and form complexes with HSA, exhibiting docking energies of -8.5 and -8.1 kcal/mol. These results support that such alkaloids are potential candidates for the treatment of Parkinson's disease.