Author | Costa, Renyer A. | |
Author | Barros, Gabriel de A. | |
Author | Silva, Jonathas N. da | |
Author | Oliveira, Kelson M. | |
Author | Bezerra, Daniel Pereira | |
Author | Soares, Milena Botelho Pereira | |
Author | Costa, Emmanoel Vilaça | |
Access date | 2021-07-05T14:01:42Z | |
Available date | 2021-07-05T14:01:42Z | |
Document date | 2021 | |
Citation | COSTA, Renyer A. et al. 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. Journal of Molecular Structure, v . 1229, 2021. | pt_BR |
ISSN | 0022-2860 | pt_BR |
URI | https://www.arca.fiocruz.br/handle/icict/47978 | |
Sponsorship | Conselho Nacional de Desenvolvi- mento Científico e Tecnológico (CNPq), Coordenação de Aperfeiçoa- mento de Pessoal de Nível Superior (CAPES) - Code 001, Finan- ciadora de Estudos e Projetos (FINEP), Fundação de Amparo àPesquisa do Estado da Bahia (FAPESB), and Federal University of Amazonas (UFAM) for financial support and fellowship | pt_BR |
Language | eng | pt_BR |
Publisher | Elsevier | pt_BR |
Rights | open access | pt_BR |
Subject in Portuguese | DFT | pt_BR |
Subject in Portuguese | Técnicas In Vitro | pt_BR |
Subject in Portuguese | Guatteria | pt_BR |
Subject in Portuguese | Dinâmica molecular | pt_BR |
Subject in Portuguese | Citotoxicidade | pt_BR |
Subject in Portuguese | DNA | pt_BR |
Title | 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 | pt_BR |
Type | Article | pt_BR |
DOI | 10.1016/j.molstruc.2020.129844 | |
Abstract | 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 geom- etry 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 vi- brations that characterize the 7,7 dimethylaporphine skeleton, besides enabling the observation of inter- molecular 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. | pt_BR |
Affilliation | Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brazil. | pt_BR |
Affilliation | University of Campinas. Chemistry institute. Campinas, SP, Brazil. | pt_BR |
Affilliation | São Paulo State University. Faculty of Sciences and Letters. São Paulo, SP, Brazil. | pt_BR |
Affilliation | Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brazil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil. | pt_BR |
Affilliation | Fundação Oswaldo Cruz. Instituto Gonçalo Moniz. Salvador, BA, Bahia, Brasil. | pt_BR |
Affilliation | Federal University of Amazonas. Department of Chemistry. Manaus, AM, Brazil. | pt_BR |
Subject | DFT | pt_BR |
Subject | 7,7-dimethylaporphine alkaloids | pt_BR |
Subject | Docking | pt_BR |
Subject | Molecular dynamics | pt_BR |
Subject | Cytotoxicity | pt_BR |
Subject | HepG2 | pt_BR |