Jesica Dimmer1, Fernanda V Cabral2, Caetano Padial Sabino3, Camila Ramos Silva2, Susana C Núñez-Montoya1, José Luis Cabrera1, Martha S Ribeiro4. 1. Instituto Multidisciplinario de Biología Vegetal (IMBIV), CONICET. Av. Vélez Sarsfield 1666. CP: X5016GCN Córdoba, Argentina; Dpto. Ciencias Farmacéuticas, Fac. Cs. Qcas. Universidad Nacional Córdoba. CP: X5000HUA Córdoba, Argentina. 2. Centro de Lasers e Aplicações, Instituto de Pesquisas Energéticas e Nucleares (IPEN-CNEN/SP) - Av. Lineu Prestes 2242, Cidade Universitária "Armando de Sales Oliveira", CEP 05508-000 São Paulo, SP, Brazil. 3. Centro de Lasers e Aplicações, Instituto de Pesquisas Energéticas e Nucleares (IPEN-CNEN/SP) - Av. Lineu Prestes 2242, Cidade Universitária "Armando de Sales Oliveira", CEP 05508-000 São Paulo, SP, Brazil; Department of Clinical Analysis, School of Pharmaceutical Sciences, University of São Paulo, São Paulo, SP, Brazil; Biolambda, Translational Biophotonics LTD, São Paulo, SP, Brazil. 4. Centro de Lasers e Aplicações, Instituto de Pesquisas Energéticas e Nucleares (IPEN-CNEN/SP) - Av. Lineu Prestes 2242, Cidade Universitária "Armando de Sales Oliveira", CEP 05508-000 São Paulo, SP, Brazil. Electronic address: marthasr@usp.br.
Abstract
BACKGROUND: Cutaneous leishmaniasis (CL) is a vector-borne disease caused by obligate protist parasites from the genus Leishmania. The potential toxicity as well as the increased resistance of standard treatments has encouraged the development of new therapeutical strategies. Photodynamic inactivation (PDI) combines the use of a photosensitizer and light to generate reactive oxygen species and kill cells, including microorganisms. Vegetal kingdom constitutes an important source of bioactive compounds that deserve to be investigated in the search of naturally occurring drugs with leishmanicidal activity. PURPOSE: The purpose of this study was to test the antiparasitic activity of PDI (ApPDI) of five natural anthraquinones (AQs) obtained from Heterophyllaea lycioides (Rusby) Sandwith (Rubiacae). To support our results, effect of AQ mediated-PDI on parasite´s morphology and AQ uptake were studied. Cytotoxicity on fibroblasts was also evaluated. STUDY DESIGN/ METHODS: Two monomers, soranjidiol (Sor) and 5-chlorosoranjidiol (5-ClSor) plus three bi-anthraquinones (bi-AQs), bisoranjidiol (Bisor), 7-chlorobisoranjidiol (7-ClBisor) and Lycionine (Lyc) were selected for this study. Recombinant L. amazonensis promastigote strain expressing luciferase was subjected to AQs and LED treatment. Following irradiation with variable light parameters, cell viability was quantified by bioluminescence. Alteration on parasite's morphology was analyzed by scanning electron microscopy (SEM). In addition, we verified the AQ uptake in Leishmania cells by fluorescence and their toxicity on fibroblasts by using MTT assay. RESULTS: Bisor, Sor and 5-ClSor exhibited photodynamic effect on L. amazonensis. SEM showed that promastigotes treated with Bisor-mediated PDI exhibited a significant alteration in shape and size. Sor and 5-ClSor presented higher uptake levels than bi-AQs (Bisor, Lyc and 7-ClBisor). Finally, Sor and Bisor presented the lowest toxic activity against fibroblasts. CONCLUSION: Taking together, our results indicate that Sor presents the highest specificity towards Leishmania cells with no toxicity on fibroblasts.
BACKGROUND:Cutaneous leishmaniasis (CL) is a vector-borne disease caused by obligate protist parasites from the genus Leishmania. The potential toxicity as well as the increased resistance of standard treatments has encouraged the development of new therapeutical strategies. Photodynamic inactivation (PDI) combines the use of a photosensitizer and light to generate reactive oxygen species and kill cells, including microorganisms. Vegetal kingdom constitutes an important source of bioactive compounds that deserve to be investigated in the search of naturally occurring drugs with leishmanicidal activity. PURPOSE: The purpose of this study was to test the antiparasitic activity of PDI (ApPDI) of five natural anthraquinones (AQs) obtained from Heterophyllaea lycioides (Rusby) Sandwith (Rubiacae). To support our results, effect of AQ mediated-PDI on parasite´s morphology and AQ uptake were studied. Cytotoxicity on fibroblasts was also evaluated. STUDY DESIGN/ METHODS: Two monomers, soranjidiol (Sor) and 5-chlorosoranjidiol (5-ClSor) plus three bi-anthraquinones (bi-AQs), bisoranjidiol (Bisor), 7-chlorobisoranjidiol (7-ClBisor) and Lycionine (Lyc) were selected for this study. Recombinant L. amazonensis promastigote strain expressing luciferase was subjected to AQs and LED treatment. Following irradiation with variable light parameters, cell viability was quantified by bioluminescence. Alteration on parasite's morphology was analyzed by scanning electron microscopy (SEM). In addition, we verified the AQ uptake in Leishmania cells by fluorescence and their toxicity on fibroblasts by using MTT assay. RESULTS:Bisor, Sor and 5-ClSor exhibited photodynamic effect on L. amazonensis. SEM showed that promastigotes treated with Bisor-mediated PDI exhibited a significant alteration in shape and size. Sor and 5-ClSor presented higher uptake levels than bi-AQs (Bisor, Lyc and 7-ClBisor). Finally, Sor and Bisor presented the lowest toxic activity against fibroblasts. CONCLUSION: Taking together, our results indicate that Sor presents the highest specificity towards Leishmania cells with no toxicity on fibroblasts.
Authors: Luiza F O Gervazoni; Gabrielle B Barcellos; Taiana Ferreira-Paes; Elmo E Almeida-Amaral Journal: Front Chem Date: 2020-11-23 Impact factor: 5.221