Experimental and theoretical study on spectral features, reactivity, solvation, topoisomerase I inhibition and in vitro cytotoxicity in human HepG2 cells of guadiscine and guadiscidine aporphine alkaloids

• Autor(a) principal: Costa, Renyer A.
• Data de Publicação: 2021
• Outros Autores: Barros, Gabriel de A., da Silva, Jonathas N. [UNESP], Oliveira, Kelson M., Bezerra, Daniel P., Soares, Milena B.P., Costa, Emmanoel V.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Institucional da UNESP
• Texto Completo: http://dx.doi.org/10.1016/j.molstruc.2020.129844; http://hdl.handle.net/11449/205695
• topic: 7,7-dimethylaporphine alkaloids; Cytotoxicity; DFT; Docking; HepG2; Molecular dynamics

In this study, guadiscine (G1) and guadiscidine (G2), 7,7-dimethylaporphine alkaloids from Guatteria friesiana, have they geometric paramaters, vibrational behavior and quantum chemical properties (HOMO-LUMO, MEP, ALIE and Fukui indices) analyzed through a theoretical view, by density functional theory (DFT), using the Becker's three-parameter hybrid exchange functional combined with the Lee–Yang–Parr correlation functional (B3LYP) and 6–311G(2d,p) and 6–311G++(2df,3p) basis sets. The obtained geometry data were compared with x-ray data for (−)-N-acetyl-anonaine, showing close values. Vibrational analysis, together with potential energy distribution (PED) calculations, revealed several characteristic vibrations that characterize the 7,7 dimethylaporphine skeleton, besides enabling the observation of intermolecular H-bonds through dimers formation. Molecular dynamic simulations were carried out, allowing to evaluate the solvation free energies of G1 and G2 in water, methanol and ethanol, as well as H-bonds formation between G1 and G2 and the tested solvents. The antineoplastic potential of the title molecules was evaluated via molecular docking calculations with topoisomerase I complexed with DNA. Guadiscine and guadiscidine showed, respectively, binding free energies of -8.0 and -8.5 kcal/mol, while topotecan, a DNA topoisomerase I inhibitor, showed a binding free energy value of -12 kcal/mol, indicating that the studied molecules are good topoisomerase I inhibitors. In vitro cytotoxicity assay with HepG2 cell line were performed, revealing significant antitumor potential for G2.