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

Detalhes bibliográficos
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
Resumo: 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.
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spelling 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 alkaloids7,7-dimethylaporphine alkaloidsCytotoxicityDFTDockingHepG2Molecular dynamicsIn 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.Department of Chemistry Federal University of Amazonas (DQ-UFAM)Chemistry institute University of CampinasFaculty of Sciences and Letters - Araraquara Campus São Paulo State University (UNESP)Gonçalo Moniz Institute Oswaldo Cruz Fundation (IGM/FIOCRUZ-BA)Faculty of Sciences and Letters - Araraquara Campus São Paulo State University (UNESP)Federal University of Amazonas (DQ-UFAM)Universidade Estadual de Campinas (UNICAMP)Universidade Estadual Paulista (Unesp)Oswaldo Cruz Fundation (IGM/FIOCRUZ-BA)Costa, Renyer A.Barros, Gabriel de A.da Silva, Jonathas N. [UNESP]Oliveira, Kelson M.Bezerra, Daniel P.Soares, Milena B.P.Costa, Emmanoel V.2021-06-25T10:19:41Z2021-06-25T10:19:41Z2021-04-05info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.molstruc.2020.129844Journal of Molecular Structure, v. 1229.0022-2860http://hdl.handle.net/11449/20569510.1016/j.molstruc.2020.1298442-s2.0-85099005983Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengJournal of Molecular Structureinfo:eu-repo/semantics/openAccess2021-10-22T13:22:18Zoai:repositorio.unesp.br:11449/205695Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T20:24:56.292825Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv 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
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
spellingShingle 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
Costa, Renyer A.
7,7-dimethylaporphine alkaloids
Cytotoxicity
DFT
Docking
HepG2
Molecular dynamics
title_short 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
title_full 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
title_fullStr 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
title_full_unstemmed 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
title_sort 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
author Costa, Renyer A.
author_facet Costa, Renyer A.
Barros, Gabriel de A.
da Silva, Jonathas N. [UNESP]
Oliveira, Kelson M.
Bezerra, Daniel P.
Soares, Milena B.P.
Costa, Emmanoel V.
author_role author
author2 Barros, Gabriel de A.
da Silva, Jonathas N. [UNESP]
Oliveira, Kelson M.
Bezerra, Daniel P.
Soares, Milena B.P.
Costa, Emmanoel V.
author2_role author
author
author
author
author
author
dc.contributor.none.fl_str_mv Federal University of Amazonas (DQ-UFAM)
Universidade Estadual de Campinas (UNICAMP)
Universidade Estadual Paulista (Unesp)
Oswaldo Cruz Fundation (IGM/FIOCRUZ-BA)
dc.contributor.author.fl_str_mv Costa, Renyer A.
Barros, Gabriel de A.
da Silva, Jonathas N. [UNESP]
Oliveira, Kelson M.
Bezerra, Daniel P.
Soares, Milena B.P.
Costa, Emmanoel V.
dc.subject.por.fl_str_mv 7,7-dimethylaporphine alkaloids
Cytotoxicity
DFT
Docking
HepG2
Molecular dynamics
topic 7,7-dimethylaporphine alkaloids
Cytotoxicity
DFT
Docking
HepG2
Molecular dynamics
description 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.
publishDate 2021
dc.date.none.fl_str_mv 2021-06-25T10:19:41Z
2021-06-25T10:19:41Z
2021-04-05
dc.type.status.fl_str_mv info:eu-repo/semantics/publishedVersion
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv http://dx.doi.org/10.1016/j.molstruc.2020.129844
Journal of Molecular Structure, v. 1229.
0022-2860
http://hdl.handle.net/11449/205695
10.1016/j.molstruc.2020.129844
2-s2.0-85099005983
url http://dx.doi.org/10.1016/j.molstruc.2020.129844
http://hdl.handle.net/11449/205695
identifier_str_mv Journal of Molecular Structure, v. 1229.
0022-2860
10.1016/j.molstruc.2020.129844
2-s2.0-85099005983
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Journal of Molecular Structure
dc.rights.driver.fl_str_mv info:eu-repo/semantics/openAccess
eu_rights_str_mv openAccess
dc.source.none.fl_str_mv Scopus
reponame:Repositório Institucional da UNESP
instname:Universidade Estadual Paulista (UNESP)
instacron:UNESP
instname_str Universidade Estadual Paulista (UNESP)
instacron_str UNESP
institution UNESP
reponame_str Repositório Institucional da UNESP
collection Repositório Institucional da UNESP
repository.name.fl_str_mv Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)
repository.mail.fl_str_mv
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