Estudo teórico e experimental em nível DFT e docking molecular para alcaloides do tipo 7,7-dimetilaporfínicos isolados de Guatteria friesiana (Annonaceae)

Abstract

Apophinoids are a class of isoquinoline alkaloids with more than 500 compounds already identified in the literature and specially recognized for having a range of pharmacological activities such as anticancer, anesthetic, vasodilator and antibacterial. Belonging to this class, the aporphine alkaloids comprise a new class titled 7,7-dimethylaporphinic (due to the presence of two methyls in C7) that until then had no theoretical data relating their structural, vibrational, quantum properties and study of molecular docking.In this context, the objective of this work was to investigate the alkaloids 9-methoxyguatterfriesine (I), (R) -6,6a-dihydro-9-methoxyguatterfriesine (II) and 4,5-dehydro-9-methoxyguatterfriesine (III), part of this new class, through a theoretical approach using DFT calculations with the B3LYP functional and 6-311G (2d, p) bases set.The geometric optimization data for the structures were compared with x-ray data for a similar structure available in the literature and obtained close bond lengths. NBO and NLO calculations were performed in order to increase the knowledge regarding the quantum properties of the substances besides explaining the effects of electronic delocalization in the structures.The theoretical UV-vis and IV spectra were compared with experimental data obtained in previous work and presented satisfactory similarities, besides confirming the existence of the dimeric form for the three compounds in solution, these forms stabilized by OH---N hydrogen bonding interactions type. A molecular docking study was performed, substance III revealed greater bioactive potential, and to compare a docking was performed for two substances (9-metoxiguatteriscineand 6,6a-diidrodemetoxiguadiscine) with a skeleton similar to molecules I, II and III, however with different substituents in the rings. In addition, an in vitro cytotoxic assay was performed in which substance III obtained the highest inhibitory power, thus indicating the reliability of theoretical molecular docking methods.