Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment

Detalhes bibliográficos
Autor(a) principal: Cardoso, Suziene Caroline Silva
Data de Publicação: 2024
Outros Autores: Cunha, Wilson R., Cavallari, Pedro S. dos S. R., Almeida, Samarah Gomes de, Januário, Ana Helena, Pauletti, Patrícia Mendonça, Santos, Fernanda Amorim, Laurentiz, Rosângela da Silva, Miranda, Giulia Stavrakas, Andrade, João Victor, Orenha, Renato Pereira, Parreira, Renato Luis Tame, Silva, Márcio Luís Andrade e, Santos, Mario F. C., Esperandim, Viviane
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Bioscience journal (Online)
Texto Completo: https://seer.ufu.br/index.php/biosciencejournal/article/view/69502
Resumo: Chagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.
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spelling Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessmentMolecular dockingNatural productsTrypanocideTrypanosoma cruzi.Health SciencesChagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.Universidade Federal de Uberlândia2024-03-15info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionapplication/pdfhttps://seer.ufu.br/index.php/biosciencejournal/article/view/6950210.14393/BJ-v40n0a2024-69502Bioscience Journal ; Vol. 40 (2024): Continuous Publication; e40016Bioscience Journal ; v. 40 (2024): Continuous Publication; e400161981-3163reponame:Bioscience journal (Online)instname:Universidade Federal de Uberlândia (UFU)instacron:UFUenghttps://seer.ufu.br/index.php/biosciencejournal/article/view/69502/38421Brazil; Contemporary Copyright (c) 2024 Suziene Caroline Silva Cardoso, Wilson R. Cunha, Pedro S. dos S. R. Cavallari, Samarah Gomes de Almeida, Ana Helena Januário, Patrícia Mendonça Pauletti, Fernanda Amorim Santos, Rosângela da Silva Laurentiz, Giulia Stavrakas Miranda, João Victor Andrade, Renato Pereira Orenha, Renato Luis Tame Parreira, Márcio Luís Andrade e Silva, Mario F. C. Santos, Viviane Esperandimhttps://creativecommons.org/licenses/by/4.0info:eu-repo/semantics/openAccessCardoso, Suziene Caroline SilvaCunha, Wilson R.Cavallari, Pedro S. dos S. R.Almeida, Samarah Gomes deJanuário, Ana HelenaPauletti, Patrícia MendonçaSantos, Fernanda AmorimLaurentiz, Rosângela da SilvaMiranda, Giulia StavrakasAndrade, João VictorOrenha, Renato PereiraParreira, Renato Luis TameSilva, Márcio Luís Andrade eSantos, Mario F. C.Esperandim, Viviane2024-04-03T20:47:42Zoai:ojs.www.seer.ufu.br:article/69502Revistahttps://seer.ufu.br/index.php/biosciencejournalPUBhttps://seer.ufu.br/index.php/biosciencejournal/oaibiosciencej@ufu.br||1981-31631516-3725opendoar:2024-04-03T20:47:42Bioscience journal (Online) - Universidade Federal de Uberlândia (UFU)false
dc.title.none.fl_str_mv Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment
title Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment
spellingShingle Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment
Cardoso, Suziene Caroline Silva
Molecular docking
Natural products
Trypanocide
Trypanosoma cruzi.
Health Sciences
title_short Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment
title_full Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment
title_fullStr Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment
title_full_unstemmed Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment
title_sort Synthesis of (-) - 6,6'-dinitrohinokinin from hinokinin natural product and in silico and in vitro trypanocidal activity assessment
author Cardoso, Suziene Caroline Silva
author_facet Cardoso, Suziene Caroline Silva
Cunha, Wilson R.
Cavallari, Pedro S. dos S. R.
Almeida, Samarah Gomes de
Januário, Ana Helena
Pauletti, Patrícia Mendonça
Santos, Fernanda Amorim
Laurentiz, Rosângela da Silva
Miranda, Giulia Stavrakas
Andrade, João Victor
Orenha, Renato Pereira
Parreira, Renato Luis Tame
Silva, Márcio Luís Andrade e
Santos, Mario F. C.
Esperandim, Viviane
author_role author
author2 Cunha, Wilson R.
Cavallari, Pedro S. dos S. R.
Almeida, Samarah Gomes de
Januário, Ana Helena
Pauletti, Patrícia Mendonça
Santos, Fernanda Amorim
Laurentiz, Rosângela da Silva
Miranda, Giulia Stavrakas
Andrade, João Victor
Orenha, Renato Pereira
Parreira, Renato Luis Tame
Silva, Márcio Luís Andrade e
Santos, Mario F. C.
Esperandim, Viviane
author2_role author
author
author
author
author
author
author
author
author
author
author
author
author
author
dc.contributor.author.fl_str_mv Cardoso, Suziene Caroline Silva
Cunha, Wilson R.
Cavallari, Pedro S. dos S. R.
Almeida, Samarah Gomes de
Januário, Ana Helena
Pauletti, Patrícia Mendonça
Santos, Fernanda Amorim
Laurentiz, Rosângela da Silva
Miranda, Giulia Stavrakas
Andrade, João Victor
Orenha, Renato Pereira
Parreira, Renato Luis Tame
Silva, Márcio Luís Andrade e
Santos, Mario F. C.
Esperandim, Viviane
dc.subject.por.fl_str_mv Molecular docking
Natural products
Trypanocide
Trypanosoma cruzi.
Health Sciences
topic Molecular docking
Natural products
Trypanocide
Trypanosoma cruzi.
Health Sciences
description Chagas disease is a public health problem affecting approximately seven million people worldwide. Thus, there is a need to discover drugs for the adequate treatment of this disease because currently available drugs have serious side effects. Therefore, this study aimed to evaluate the in vitro trypanocidal activity of (-)-6,6'-dinitrohinokinin, obtained from the partial synthesis of (-)-hinokinin, on the trypomastigotes and amastigotes forms. For the trypomastigote assay, blood was collected from mice infected with Trypanosoma cruzi through cardiac puncture at the parasitemic peak. The results show that (-)-6,6'-dinitrohinokinin was effective against the trypomastigote forms, presenting an IC50 of 19.83 µM and lysis percentage values ​​of 78.4% and 69.4% at concentrations of 200 and 100 µM, respectively. Molecular docking calculations indicate that (-)-6,6'-dinitrohinokinin favorably interacts with the amino acids present in the active site of the protein trypanothione reductase, a typical target for anti-trypanosomal drug development. According to the results, the (-)-6,6'-dinitrohinokinin showed more significant trypanocidal activity with IC50 of 1.83 µM than benzonidazole positive control with IC50 of 53.2 µM, showing to be a prototype molecule promising for the development of a new antiparasitic drug.
publishDate 2024
dc.date.none.fl_str_mv 2024-03-15
dc.type.driver.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
format article
status_str publishedVersion
dc.identifier.uri.fl_str_mv https://seer.ufu.br/index.php/biosciencejournal/article/view/69502
10.14393/BJ-v40n0a2024-69502
url https://seer.ufu.br/index.php/biosciencejournal/article/view/69502
identifier_str_mv 10.14393/BJ-v40n0a2024-69502
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv https://seer.ufu.br/index.php/biosciencejournal/article/view/69502/38421
dc.rights.driver.fl_str_mv https://creativecommons.org/licenses/by/4.0
info:eu-repo/semantics/openAccess
rights_invalid_str_mv https://creativecommons.org/licenses/by/4.0
eu_rights_str_mv openAccess
dc.format.none.fl_str_mv application/pdf
dc.coverage.none.fl_str_mv Brazil; Contemporary
dc.publisher.none.fl_str_mv Universidade Federal de Uberlândia
publisher.none.fl_str_mv Universidade Federal de Uberlândia
dc.source.none.fl_str_mv Bioscience Journal ; Vol. 40 (2024): Continuous Publication; e40016
Bioscience Journal ; v. 40 (2024): Continuous Publication; e40016
1981-3163
reponame:Bioscience journal (Online)
instname:Universidade Federal de Uberlândia (UFU)
instacron:UFU
instname_str Universidade Federal de Uberlândia (UFU)
instacron_str UFU
institution UFU
reponame_str Bioscience journal (Online)
collection Bioscience journal (Online)
repository.name.fl_str_mv Bioscience journal (Online) - Universidade Federal de Uberlândia (UFU)
repository.mail.fl_str_mv biosciencej@ufu.br||
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