Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy

Detalhes bibliográficos
Autor(a) principal: Linares, Irwin A.P.
Data de Publicação: 2020
Outros Autores: Velásquez, Angela M.A. [UNESP], Graminha, Marcia A.S. [UNESP], de Oliveira, Kleber T., Perussi, Janice Rodrigues
Tipo de documento: Artigo
Idioma: eng
Título da fonte: Repositório Institucional da UNESP
Texto Completo: http://dx.doi.org/10.1016/j.pdpdt.2020.101769
http://hdl.handle.net/11449/198843
Resumo: Leishmaniasis is a serious and neglected disease that affects 14 million people around the World. The currently available drugs for treatment present several drawbacks such as low efficacy and severe side effects, contributing to patients’ low compliance. Photodynamic therapy (PDT) is rising as a promising treatment of cutaneous leishmaniasis, mainly considering its topical administration that circumvents any potential adverse effects commonly related to oral/parenteral administration. PDT depends on the interaction between a light-sensitive compound (photosensitizer - PS), light and molecular oxygen. The reaction generates reactive oxygen species (ROS) which induce cell death by oxidative stress. The main goal of this study is to demonstrate the antileishmanial effect of three chlorin derivatives (CHL-OH-A, CHL-OH-B, CHL-TRISMA) using PDT, as well as to investigate their cell death pathway on Leishmania amazonensis promastigote forms after chlorin-PDT application. The chlorin derivatives herein studied did not exhibit aggregates in aqueous medium and showed fast accumulation in Leishmania acidic compartments. CHL-OH-A exhibited the highest antiparasitic activity at 24 h (0.33 μmol L−1) and 48 h (0.14 μmol L−1) after irradiation at 660 nm (6.0 Jcm-2). CHL-OH-A, CHL-OH-B and CHL-TRISMA molecules induced the cell death of parasites mainly by an apoptotic-like process in the presence of light. These chlorin derivatives are 80-fold more active against Leishmania when compared to other PSs reported in the literature. In this study, we have shown that these amphiphilic chlorins, and in particular, CHL-OH-A, exert an interesting leishmanicidal activity suggesting that the use of these PSs associated with PDT could be a promising strategy for treatment of cutaneous leishmaniasis.
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spelling Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapyCell deathChlorin derivativesLeishmania acidic compartmentsLeishmania amazonensisPhotodynamic therapyPhotosensitizerLeishmaniasis is a serious and neglected disease that affects 14 million people around the World. The currently available drugs for treatment present several drawbacks such as low efficacy and severe side effects, contributing to patients’ low compliance. Photodynamic therapy (PDT) is rising as a promising treatment of cutaneous leishmaniasis, mainly considering its topical administration that circumvents any potential adverse effects commonly related to oral/parenteral administration. PDT depends on the interaction between a light-sensitive compound (photosensitizer - PS), light and molecular oxygen. The reaction generates reactive oxygen species (ROS) which induce cell death by oxidative stress. The main goal of this study is to demonstrate the antileishmanial effect of three chlorin derivatives (CHL-OH-A, CHL-OH-B, CHL-TRISMA) using PDT, as well as to investigate their cell death pathway on Leishmania amazonensis promastigote forms after chlorin-PDT application. The chlorin derivatives herein studied did not exhibit aggregates in aqueous medium and showed fast accumulation in Leishmania acidic compartments. CHL-OH-A exhibited the highest antiparasitic activity at 24 h (0.33 μmol L−1) and 48 h (0.14 μmol L−1) after irradiation at 660 nm (6.0 Jcm-2). CHL-OH-A, CHL-OH-B and CHL-TRISMA molecules induced the cell death of parasites mainly by an apoptotic-like process in the presence of light. These chlorin derivatives are 80-fold more active against Leishmania when compared to other PSs reported in the literature. In this study, we have shown that these amphiphilic chlorins, and in particular, CHL-OH-A, exert an interesting leishmanicidal activity suggesting that the use of these PSs associated with PDT could be a promising strategy for treatment of cutaneous leishmaniasis.Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)Instituto de Química de São Carlos Universidade de São PauloUniversidade Estadual Paulista (UNESP) Faculdade de Ciências FarmacêuticasDepartamento de Química Universidade Federal de São CarlosUniversidade Estadual Paulista (UNESP) Faculdade de Ciências FarmacêuticasUniversidade de São Paulo (USP)Universidade Estadual Paulista (Unesp)Universidade Federal de São Carlos (UFSCar)Linares, Irwin A.P.Velásquez, Angela M.A. [UNESP]Graminha, Marcia A.S. [UNESP]de Oliveira, Kleber T.Perussi, Janice Rodrigues2020-12-12T01:23:26Z2020-12-12T01:23:26Z2020-09-01info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articlehttp://dx.doi.org/10.1016/j.pdpdt.2020.101769Photodiagnosis and Photodynamic Therapy, v. 31.1873-15971572-1000http://hdl.handle.net/11449/19884310.1016/j.pdpdt.2020.1017692-s2.0-85084826751Scopusreponame:Repositório Institucional da UNESPinstname:Universidade Estadual Paulista (UNESP)instacron:UNESPengPhotodiagnosis and Photodynamic Therapyinfo:eu-repo/semantics/openAccess2021-10-22T20:42:34Zoai:repositorio.unesp.br:11449/198843Repositório InstitucionalPUBhttp://repositorio.unesp.br/oai/requestopendoar:29462024-08-05T14:38:49.483821Repositório Institucional da UNESP - Universidade Estadual Paulista (UNESP)false
dc.title.none.fl_str_mv Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy
title Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy
spellingShingle Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy
Linares, Irwin A.P.
Cell death
Chlorin derivatives
Leishmania acidic compartments
Leishmania amazonensis
Photodynamic therapy
Photosensitizer
title_short Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy
title_full Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy
title_fullStr Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy
title_full_unstemmed Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy
title_sort Antileishmanial activity of amphiphilic chlorin derivatives mediated by photodynamic therapy
author Linares, Irwin A.P.
author_facet Linares, Irwin A.P.
Velásquez, Angela M.A. [UNESP]
Graminha, Marcia A.S. [UNESP]
de Oliveira, Kleber T.
Perussi, Janice Rodrigues
author_role author
author2 Velásquez, Angela M.A. [UNESP]
Graminha, Marcia A.S. [UNESP]
de Oliveira, Kleber T.
Perussi, Janice Rodrigues
author2_role author
author
author
author
dc.contributor.none.fl_str_mv Universidade de São Paulo (USP)
Universidade Estadual Paulista (Unesp)
Universidade Federal de São Carlos (UFSCar)
dc.contributor.author.fl_str_mv Linares, Irwin A.P.
Velásquez, Angela M.A. [UNESP]
Graminha, Marcia A.S. [UNESP]
de Oliveira, Kleber T.
Perussi, Janice Rodrigues
dc.subject.por.fl_str_mv Cell death
Chlorin derivatives
Leishmania acidic compartments
Leishmania amazonensis
Photodynamic therapy
Photosensitizer
topic Cell death
Chlorin derivatives
Leishmania acidic compartments
Leishmania amazonensis
Photodynamic therapy
Photosensitizer
description Leishmaniasis is a serious and neglected disease that affects 14 million people around the World. The currently available drugs for treatment present several drawbacks such as low efficacy and severe side effects, contributing to patients’ low compliance. Photodynamic therapy (PDT) is rising as a promising treatment of cutaneous leishmaniasis, mainly considering its topical administration that circumvents any potential adverse effects commonly related to oral/parenteral administration. PDT depends on the interaction between a light-sensitive compound (photosensitizer - PS), light and molecular oxygen. The reaction generates reactive oxygen species (ROS) which induce cell death by oxidative stress. The main goal of this study is to demonstrate the antileishmanial effect of three chlorin derivatives (CHL-OH-A, CHL-OH-B, CHL-TRISMA) using PDT, as well as to investigate their cell death pathway on Leishmania amazonensis promastigote forms after chlorin-PDT application. The chlorin derivatives herein studied did not exhibit aggregates in aqueous medium and showed fast accumulation in Leishmania acidic compartments. CHL-OH-A exhibited the highest antiparasitic activity at 24 h (0.33 μmol L−1) and 48 h (0.14 μmol L−1) after irradiation at 660 nm (6.0 Jcm-2). CHL-OH-A, CHL-OH-B and CHL-TRISMA molecules induced the cell death of parasites mainly by an apoptotic-like process in the presence of light. These chlorin derivatives are 80-fold more active against Leishmania when compared to other PSs reported in the literature. In this study, we have shown that these amphiphilic chlorins, and in particular, CHL-OH-A, exert an interesting leishmanicidal activity suggesting that the use of these PSs associated with PDT could be a promising strategy for treatment of cutaneous leishmaniasis.
publishDate 2020
dc.date.none.fl_str_mv 2020-12-12T01:23:26Z
2020-12-12T01:23:26Z
2020-09-01
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.pdpdt.2020.101769
Photodiagnosis and Photodynamic Therapy, v. 31.
1873-1597
1572-1000
http://hdl.handle.net/11449/198843
10.1016/j.pdpdt.2020.101769
2-s2.0-85084826751
url http://dx.doi.org/10.1016/j.pdpdt.2020.101769
http://hdl.handle.net/11449/198843
identifier_str_mv Photodiagnosis and Photodynamic Therapy, v. 31.
1873-1597
1572-1000
10.1016/j.pdpdt.2020.101769
2-s2.0-85084826751
dc.language.iso.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv Photodiagnosis and Photodynamic Therapy
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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