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

• Published in: Journal of molecular structure 2021-04, Vol.1229, p.129844, Article 129844
• Main Authors: Costa, Renyer A., Barros, Gabriel de A., da Silva, Jonathas N., Oliveira, Kelson M., Bezerra, Daniel P., Soares, Milena B.P., Costa, Emmanoel V.
• Format: Article
• Language: English
• Subjects: 7,7-dimethylaporphine alkaloids; Cytotoxicity; DFT; Docking; HepG2; Molecular dynamics
• ISSN: 0022-2860; 1872-8014
• DOI: 10.1016/j.molstruc.2020.129844

•Homo-Lumo energy gap and global reactive parameters were calculated.•MEP, ALIE and Fukui indices calculations indicate the most reactive regions of the alkaloids guadiscine and guadiscidine.•The comparison between theoretical and experimental IR spectra allowed to visualize intermolecular H-Bonds formation through dimer formation.•Solvation free energies were calculated in different solvents.•Cytotoxicity assay performed with guadiscidine revealed great activity against HepG2 cell line. 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.