Isobruceína B e neosergeolida: modelagem em nível de DFT e estudos de docking molecular com Dihidrofolato Redutase de Plasmodium vivax

Abstract

The quassinoids are highly oxygenated terpenoids produced only by species of the family Simaroubaceae. The quassionoids isobrucein B and neosergeolide have experimentally proven antitumor and antimalarial activities. Nevertheless, isobrucein B and neosergeolide have high cytotoxicity values, they affect both neoplastic cells and healthy cells, acting in the same way against malaria plasmodium and healthy cells. Due to this situation it is necessary to use molecular docking, which is a computational procedure capable of predicting the best orientation and binding between two molecules. Docking indicates a pathway for drug development and helps through conformations decrease cytotoxicity problems. In this context, a study combining quantum and experimental data on the density functional theory (DFT) of the structural, vibrational and electronic properties of isobrucein b and neosergeolid are presented. To obtain the results, the base function 6-311G (2d, p) and the exchange and correlation functional introduced by Axel Becke using the Lee-Yang-Parr (B3LYP) parameters were used. The theoretical energy optimization data were compared with the X-ray data for a similar structure in the associated literature, showing close values. The calculated HOMO-LUMO gap values show that isobrucein b and neosergeolid are soft (reactive) molecule whose values is 4.96 (e.V) and 4.63 (e.V) respectively and is directly related to the quantum and physicochemical properties of both molecules. By checking the studies of IR (Infrared) and MEPS (Electrostatic potential maps) it is possible to identify a possible formation of intermolecular dimer in isobrucein B, and this dimeric form is stabilized through hydrogen bonds that revealed several characteristic vibrations to the structure. The molecular docking study with Plasmodium vivax Dihydrofolate Reductase complex showed free binding energies of -8.3 kcal / mol for isobrucein B and -9,3 kcal/mol for neosergeolid, and this suggests that neosergeolid can be considered a good leader compound in the development of new inhibitors of DHFR than pyrimethamine, used for the treatment of malaria, the binding free energy ΔG presented a value of -7.5 kcal / mol.