Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis
| Autor(a) principal: | |
|---|---|
| Data de Publicação: | 2022 |
| Outros Autores: | , , , , , , , , , , , , |
| Tipo de documento: | Artigo |
| Idioma: | por |
| Título da fonte: | Repositório Institucional da FIOCRUZ (ARCA) |
| Texto Completo: | https://www.arca.fiocruz.br/handle/icict/56069 |
Resumo: | Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Laboratório de Síntese de Moléculas Medicinais. Londrina, PR, Brasil. |
| id |
CRUZ_f3f50da0617bac12798c73cee69b8c9f |
|---|---|
| oai_identifier_str |
oai:www.arca.fiocruz.br:icict/56069 |
| network_acronym_str |
CRUZ |
| network_name_str |
Repositório Institucional da FIOCRUZ (ARCA) |
| repository_id_str |
2135 |
| spelling |
Santiago-Silva, Kaio Maciel deBortoleti, Bruna Taciane da SilvaOliveira, Laudicéa do NascimentoMaia, Fernanda Lima de AzevedoCastro, Joyce CristinaCosta, Ivete ConchonLazarin, Danielle BidóiaWardell, James L.Wardell, Solange M. S. V.Albuquerque, Magaly GirãoLima, Camilo Henrique da SilvaPavanelli, Wander RogérioBispo, Marcelle de Lima FerreiraGonçalves, Raoni Schroeder B.2022-12-19T16:12:10Z2022-12-19T16:12:10Z2022SANTIAGO-SILVA, Kaio Maciel de et al. Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis. Antibiotics, v. 11, n. 1402, p. 1–23, 2022.2079-6382https://www.arca.fiocruz.br/handle/icict/56069porMDPI4,8-dimethoxynaphthalenylLeishmaniasisNeglected DiseasesTrypanosomatidsTrypanothione reductaseArginasaEnfermedades DesatendidasMaladies négligéesArginaseLeishmanioseDoenças NegligenciadasAntileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensisinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleUniversidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Laboratório de Síntese de Moléculas Medicinais. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil. / Fundação Oswaldo Cruz. Instituto Carlos Chagas. Programa de Pós-Graduação em Biociências e Biotecnologia. Curitiba, PR, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Department of Chemistry. University of Aberdeen. Aberdeen, Scotland, UK.CHEMSOL. Aberdeen, Scotland, UK.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Universidade Estadual de Londrina. Centro de Ciências Biológicas. Departamento de Ciências Patológicas. Laboratório de Imunoparasitologia de Doenças Negligenciadas e Câncer. Londrina, PR, Brasil.Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Laboratório de Síntese de Moléculas Medicinais. Londrina, PR, Brasil.Universidade Federal do Rio de Janeiro. Instituto de Química. Rio de Janeiro, RJ, Brasil.Leishmaniasis is a neglected tropical disease caused by Leishmania species. Available therapeutic options have several limitations. The drive to develop new, more potent, and selective antileishmanial agents is thus a major goal. Herein we report the synthesis and the biological activity evaluation against promastigote and amastigote forms of Leishmania amazonensis of nine 4,8-dimethoxynaphthalenyl chalcones. Compound ((E)-1-(4,8-dimethoxynaphthalen-1-yl)-3-(4- nitrophenyl)prop-2-en-1-one), 4f, was the most promising with an IC50 = 3.3 ± 0.34 µM (promastigotes), a low cytotoxicity profile (CC50 = 372.9 ± 0.04 µM), and a high selectivity index (SI = 112.6). Furthermore, 4f induced several morphological and ultrastructural changes in the free promastigote forms, loss of plasma membrane integrity, and increased reactive oxygen species (ROS). An in silico analysis of drug-likeness and ADME parameters suggested high oral bioavailability and intestinal absorption. Compound 4f reduced the number of infected macrophages and the number of amastigotes per macrophage, with an IC50 value of 18.5 ± 1.19 µM. Molecular docking studies with targets, ARG and TR, showed that compound 4f had more hydrogen bond interactions with the ARG enzyme, indicating a more stable protein-ligand binding. These results suggest that 4,8- dimethoxynaphthalenyl chalcones are worthy of further study as potential antileishmanial drugsinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da FIOCRUZ (ARCA)instname:Fundação Oswaldo Cruz (FIOCRUZ)instacron:FIOCRUZLICENSElicense.txtlicense.txttext/plain; charset=utf-82991https://www.arca.fiocruz.br/bitstream/icict/56069/1/license.txt5a560609d32a3863062d77ff32785d58MD51ORIGINALantibiotics-11-01402ok.pdfantibiotics-11-01402ok.pdfapplication/pdf7173006https://www.arca.fiocruz.br/bitstream/icict/56069/2/antibiotics-11-01402ok.pdf7f5a3bd1978183aeac7e9a1f03c10fe4MD52icict/560692022-12-19 13:12:11.532oai:www.arca.fiocruz.br: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ório InstitucionalPUBhttps://www.arca.fiocruz.br/oai/requestrepositorio.arca@fiocruz.bropendoar:21352022-12-19T16:12:11Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ)false |
| dc.title.en_US.fl_str_mv |
Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis |
| title |
Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis |
| spellingShingle |
Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis Santiago-Silva, Kaio Maciel de 4,8-dimethoxynaphthalenyl Leishmaniasis Neglected Diseases Trypanosomatids Trypanothione reductase Arginasa Enfermedades Desatendidas Maladies négligées Arginase Leishmaniose Doenças Negligenciadas |
| title_short |
Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis |
| title_full |
Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis |
| title_fullStr |
Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis |
| title_full_unstemmed |
Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis |
| title_sort |
Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis |
| author |
Santiago-Silva, Kaio Maciel de |
| author_facet |
Santiago-Silva, Kaio Maciel de Bortoleti, Bruna Taciane da Silva Oliveira, Laudicéa do Nascimento Maia, Fernanda Lima de Azevedo Castro, Joyce Cristina Costa, Ivete Conchon Lazarin, Danielle Bidóia Wardell, James L. Wardell, Solange M. S. V. Albuquerque, Magaly Girão Lima, Camilo Henrique da Silva Pavanelli, Wander Rogério Bispo, Marcelle de Lima Ferreira Gonçalves, Raoni Schroeder B. |
| author_role |
author |
| author2 |
Bortoleti, Bruna Taciane da Silva Oliveira, Laudicéa do Nascimento Maia, Fernanda Lima de Azevedo Castro, Joyce Cristina Costa, Ivete Conchon Lazarin, Danielle Bidóia Wardell, James L. Wardell, Solange M. S. V. Albuquerque, Magaly Girão Lima, Camilo Henrique da Silva Pavanelli, Wander Rogério Bispo, Marcelle de Lima Ferreira Gonçalves, Raoni Schroeder B. |
| author2_role |
author author author author author author author author author author author author author |
| dc.contributor.author.fl_str_mv |
Santiago-Silva, Kaio Maciel de Bortoleti, Bruna Taciane da Silva Oliveira, Laudicéa do Nascimento Maia, Fernanda Lima de Azevedo Castro, Joyce Cristina Costa, Ivete Conchon Lazarin, Danielle Bidóia Wardell, James L. Wardell, Solange M. S. V. Albuquerque, Magaly Girão Lima, Camilo Henrique da Silva Pavanelli, Wander Rogério Bispo, Marcelle de Lima Ferreira Gonçalves, Raoni Schroeder B. |
| dc.subject.other.en_US.fl_str_mv |
4,8-dimethoxynaphthalenyl |
| topic |
4,8-dimethoxynaphthalenyl Leishmaniasis Neglected Diseases Trypanosomatids Trypanothione reductase Arginasa Enfermedades Desatendidas Maladies négligées Arginase Leishmaniose Doenças Negligenciadas |
| dc.subject.en.en_US.fl_str_mv |
Leishmaniasis Neglected Diseases Trypanosomatids Trypanothione reductase |
| dc.subject.es.en_US.fl_str_mv |
Arginasa Enfermedades Desatendidas |
| dc.subject.fr.en_US.fl_str_mv |
Maladies négligées |
| dc.subject.decs.en_US.fl_str_mv |
Arginase Leishmaniose Doenças Negligenciadas |
| description |
Universidade Estadual de Londrina. Centro de Ciências Exatas. Departamento de Química. Laboratório de Síntese de Moléculas Medicinais. Londrina, PR, Brasil. |
| publishDate |
2022 |
| dc.date.accessioned.fl_str_mv |
2022-12-19T16:12:10Z |
| dc.date.available.fl_str_mv |
2022-12-19T16:12:10Z |
| dc.date.issued.fl_str_mv |
2022 |
| 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.citation.fl_str_mv |
SANTIAGO-SILVA, Kaio Maciel de et al. Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis. Antibiotics, v. 11, n. 1402, p. 1–23, 2022. |
| dc.identifier.uri.fl_str_mv |
https://www.arca.fiocruz.br/handle/icict/56069 |
| dc.identifier.issn.en_US.fl_str_mv |
2079-6382 |
| identifier_str_mv |
SANTIAGO-SILVA, Kaio Maciel de et al. Antileishmanial activity of 4,8-dimethoxynaphthalenyl chalcones on Leishmania amazonensis. Antibiotics, v. 11, n. 1402, p. 1–23, 2022. 2079-6382 |
| url |
https://www.arca.fiocruz.br/handle/icict/56069 |
| dc.language.iso.fl_str_mv |
por |
| language |
por |
| dc.rights.driver.fl_str_mv |
info:eu-repo/semantics/openAccess |
| eu_rights_str_mv |
openAccess |
| dc.publisher.none.fl_str_mv |
MDPI |
| publisher.none.fl_str_mv |
MDPI |
| dc.source.none.fl_str_mv |
reponame:Repositório Institucional da FIOCRUZ (ARCA) instname:Fundação Oswaldo Cruz (FIOCRUZ) instacron:FIOCRUZ |
| instname_str |
Fundação Oswaldo Cruz (FIOCRUZ) |
| instacron_str |
FIOCRUZ |
| institution |
FIOCRUZ |
| reponame_str |
Repositório Institucional da FIOCRUZ (ARCA) |
| collection |
Repositório Institucional da FIOCRUZ (ARCA) |
| bitstream.url.fl_str_mv |
https://www.arca.fiocruz.br/bitstream/icict/56069/1/license.txt https://www.arca.fiocruz.br/bitstream/icict/56069/2/antibiotics-11-01402ok.pdf |
| bitstream.checksum.fl_str_mv |
5a560609d32a3863062d77ff32785d58 7f5a3bd1978183aeac7e9a1f03c10fe4 |
| bitstream.checksumAlgorithm.fl_str_mv |
MD5 MD5 |
| repository.name.fl_str_mv |
Repositório Institucional da FIOCRUZ (ARCA) - Fundação Oswaldo Cruz (FIOCRUZ) |
| repository.mail.fl_str_mv |
repositorio.arca@fiocruz.br |
| _version_ |
1798324699008073728 |