Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.

Detalhes bibliográficos
Autor(a) principal: Venturini, Tarcieli Pozzebon
Data de Publicação: 2016
Tipo de documento: Tese
Idioma: por
Título da fonte: Biblioteca Digital de Teses e Dissertações do UFSM
Texto Completo: http://repositorio.ufsm.br/handle/1/18081
Resumo: The genus Fusarium is characterized by hyaline filamentous fungi that cause a wide spectrum of infections predominantly in immunocompromised patients. Disseminated fusariosis results in high rates of morbidity and mortality, since it is of difficult prevention and treatment. The remarkable primary resistance to conventional antifungals of this genus requires the search for new therapeutic possibilities. A possible attempt is the combination of antifungals and chemosensitizing agents with different mechanisms of action. This study aimed to evaluate the in vitro susceptibility of Fusarium to conventional antifungal agents (amphotericin B, itraconazole, voriconazole and caspofungin); organoselenium compounds (diphenyl diselenide and ebselen), nonantifungal drugs (amiodarone, doxycycline, moxifloxacin, pentamidine, polymyxin B, tigecycline and tobramycin), and phytocompounds (cinnamaldehyde, carvacrol and thymol), through broth microdilution method (M38-A2, CLSI). The combinations between the antifungal agents and chemosensitizers were assessed through the checkerboard technique. Among the antifungals tested amphotericin B showed greater activity in vitro (0.25-8 μg/ml); followed by voriconazole (1-16 μg/ml), itraconazole (>16 μg/ml) and caspofungin (>32 μg/ml). Diphenyl diselenide (4-32 μg/ml), ebselen (2-8 μg/ml), pentamidine (4-32 μg/ml) and polymyxin B (4-16 μg/ml) also showed antifungal activity against Fusarium spp. Ebselen and diphenyl diselenide presented high rates of synergism in combination with amphotericin B (88% and 72%, respectively) or voriconazole (80% e 64%, respectively). Combinations with nonantifungal drugs have also resulted in synergism, highlighting the following associations (% of synergism): tobramycin + amphotericin B (80%) or voriconazole (76%); polymyxin B + amphotericin B (76%) or voriconazole (64%); pentamidine + amphotericin B (72%) or voriconazole (68%); amiodarone + amphotericin B (64%) or voriconazole (76%); and moxifloxacin + amphotericin B (72%) or voriconazole (60%). Furthermore, the phytocompounds thymol and carvacrol have showed potent chemosensitizer activity in association to caspofungin (96% e 88%, respectively). Among all the tested combinations, no antagonistic interactions were observed. In conclusion, the most relevant combinations deserve a future investigation in vivo experimental models, since these associations suggest new potencial candidates for combined therapy against fusariosis.
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spelling 2019-08-29T20:38:52Z2019-08-29T20:38:52Z2016-03-24http://repositorio.ufsm.br/handle/1/18081The genus Fusarium is characterized by hyaline filamentous fungi that cause a wide spectrum of infections predominantly in immunocompromised patients. Disseminated fusariosis results in high rates of morbidity and mortality, since it is of difficult prevention and treatment. The remarkable primary resistance to conventional antifungals of this genus requires the search for new therapeutic possibilities. A possible attempt is the combination of antifungals and chemosensitizing agents with different mechanisms of action. This study aimed to evaluate the in vitro susceptibility of Fusarium to conventional antifungal agents (amphotericin B, itraconazole, voriconazole and caspofungin); organoselenium compounds (diphenyl diselenide and ebselen), nonantifungal drugs (amiodarone, doxycycline, moxifloxacin, pentamidine, polymyxin B, tigecycline and tobramycin), and phytocompounds (cinnamaldehyde, carvacrol and thymol), through broth microdilution method (M38-A2, CLSI). The combinations between the antifungal agents and chemosensitizers were assessed through the checkerboard technique. Among the antifungals tested amphotericin B showed greater activity in vitro (0.25-8 μg/ml); followed by voriconazole (1-16 μg/ml), itraconazole (>16 μg/ml) and caspofungin (>32 μg/ml). Diphenyl diselenide (4-32 μg/ml), ebselen (2-8 μg/ml), pentamidine (4-32 μg/ml) and polymyxin B (4-16 μg/ml) also showed antifungal activity against Fusarium spp. Ebselen and diphenyl diselenide presented high rates of synergism in combination with amphotericin B (88% and 72%, respectively) or voriconazole (80% e 64%, respectively). Combinations with nonantifungal drugs have also resulted in synergism, highlighting the following associations (% of synergism): tobramycin + amphotericin B (80%) or voriconazole (76%); polymyxin B + amphotericin B (76%) or voriconazole (64%); pentamidine + amphotericin B (72%) or voriconazole (68%); amiodarone + amphotericin B (64%) or voriconazole (76%); and moxifloxacin + amphotericin B (72%) or voriconazole (60%). Furthermore, the phytocompounds thymol and carvacrol have showed potent chemosensitizer activity in association to caspofungin (96% e 88%, respectively). Among all the tested combinations, no antagonistic interactions were observed. In conclusion, the most relevant combinations deserve a future investigation in vivo experimental models, since these associations suggest new potencial candidates for combined therapy against fusariosis.O gênero Fusarium é caracterizado por fungos filamentosos hialinos que causam um amplo espectro de infecções predominantemente em pacientes imunocomprometidos. A fusariose disseminada resulta em elevados índices de morbidade e mortalidade, sendo uma infecção de difícil prevenção e tratamento. A marcante resistência primária deste gênero aos antifúngicos convencionais impõe a busca por novas possibilidades terapêuticas. Uma alternativa é a combinação entre agentes antifúngicos e quimiossensibilizantes com diferentes mecanismos de ação. Este estudo objetivou avaliar a suscetibilidade in vitro de espécies de Fusarium a antifúngicos convencionais (anfotericina B, itraconazol, voriconazol e caspofungina), compostos orgânicos de selênio (disseleneto de difenila e ebselen), fármacos não antifúngicos (amiodarona, doxiciclina, moxifloxacina, pentamidina, polimixina B, tigeciclina e tobramicina) e fitocompostos (cinamaldeído, carvacrol e timol), através do método de microdiluição em caldo (M38-A2, CLSI). As combinações entre os agentes antifúngicos e quimiossensibilizantes foram avaliadas através da técnica de checkerboard. Entre os antifúngicos testados, a anfotericina B demonstrou maior atividade in vitro (0,25-8 μg/ml); seguida pelo voriconazol (1-16 μg/ml), itraconazol (>16 μg/ml) e caspofungina (>32 μg/ml). O disseleneto de difenila (4-32 μg/ml), ebselen (2-8 μg/ml), pentamidina (4-32 μg/ml) e polimixina B (4-16 μg/ml) também demonstraram atividade antifúngica contra Fusarium spp. Ebselen e disseleneto de difenila apresentaram altas taxas de sinergismos em combinação com anfotericina B (88% e 72%, respectivamente) ou voriconazol (80% e 64%, respectivamente). As combinações com fármacos não antifúngicos também resultaram em sinergismos, destacando-se as seguintes associações (% de sinergismo): tobramicina + anfotericina B (80%) ou voriconazol (76%); polimixina B + anfotericina B (76%) ou voriconazol (64%); pentamidina + anfotericina B (72%) ou voriconazol (68%); amiodarona + anfotericina B (64%) ou voriconazol (76%); e moxifloxacina + anfotericina B (72%) ou voriconazol (60%). Além disso, os fitocompostos, timol e carvacrol demonstraram potente atividade quimiossensibilizante em associação com caspofungina (96% e 88%, respectivamente). Entre todas as combinações testadas não foram observadas interações antagônicas. Em conclusão, as combinações mais relevantes merecem uma futura investigação em modelos experimentais in vivo, pois estas associações apontam novos candidatos potenciais para a terapia combinada da fusariose.Fundação de Amparo à Pesquisa do Estado do Rio Grande do Sul.porUniversidade Federal de Santa MariaCentro de Ciências da SaúdePrograma de Pós-Graduação em Ciências FarmacêuticasUFSMBrasilFarmacologiaAttribution-NonCommercial-NoDerivatives 4.0 Internationalhttp://creativecommons.org/licenses/by-nc-nd/4.0/info:eu-repo/semantics/openAccessSuscetibilidadeQuimissensibilizantesAssociaçõesAntifúngicosSinergismoFusarium spp.SusceptibilityChemosensitizersAssociationsAntifungalsSynergismCNPQ::CIENCIAS DA SAUDE::FARMACIAQuimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.Synthetic and natural chemosensitizers associated with conventional antifungals against Fusarium spp.info:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/doctoralThesisAlves, Sydney Hartzhttp://lattes.cnpq.br/0330782478769631Fuentefria, Alexandre Meneghellohttp://lattes.cnpq.br/3011308324416888Lopes, Paulo Guilherme Markushttp://lattes.cnpq.br/0280182736721337Trindade, Priscila de Arrudahttp://lattes.cnpq.br/0124362929241308http://lattes.cnpq.br/4390852722353821Venturini, Tarcieli Pozzebon400300000005600bfe6016c-9c1e-42ca-ab1d-db5453ed090cc0b26698-69fc-4115-a19f-73c221213313edc762e8-b952-4bb7-8fe6-424a950bac8c6a3b4699-c76a-4ced-9819-9d81d5aa4fc143546305-915c-443c-8ae5-09b88645907ereponame:Biblioteca Digital de Teses e Dissertações do UFSMinstname:Universidade Federal de Santa Maria (UFSM)instacron:UFSMCC-LICENSElicense_rdflicense_rdfapplication/rdf+xml; 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dc.title.por.fl_str_mv Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.
dc.title.alternative.eng.fl_str_mv Synthetic and natural chemosensitizers associated with conventional antifungals against Fusarium spp.
title Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.
spellingShingle Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.
Venturini, Tarcieli Pozzebon
Suscetibilidade
Quimissensibilizantes
Associações
Antifúngicos
Sinergismo
Fusarium spp.
Susceptibility
Chemosensitizers
Associations
Antifungals
Synergism
CNPQ::CIENCIAS DA SAUDE::FARMACIA
title_short Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.
title_full Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.
title_fullStr Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.
title_full_unstemmed Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.
title_sort Quimiossensibilizantes sintéticos e naturais associados a antifúngicos convencionais frente a Fusarium spp.
author Venturini, Tarcieli Pozzebon
author_facet Venturini, Tarcieli Pozzebon
author_role author
dc.contributor.advisor1.fl_str_mv Alves, Sydney Hartz
dc.contributor.advisor1Lattes.fl_str_mv http://lattes.cnpq.br/0330782478769631
dc.contributor.referee1.fl_str_mv Fuentefria, Alexandre Meneghello
dc.contributor.referee1Lattes.fl_str_mv http://lattes.cnpq.br/3011308324416888
dc.contributor.referee2.fl_str_mv Lopes, Paulo Guilherme Markus
dc.contributor.referee2Lattes.fl_str_mv http://lattes.cnpq.br/0280182736721337
dc.contributor.referee3.fl_str_mv Trindade, Priscila de Arruda
dc.contributor.referee3Lattes.fl_str_mv http://lattes.cnpq.br/0124362929241308
dc.contributor.authorLattes.fl_str_mv http://lattes.cnpq.br/4390852722353821
dc.contributor.author.fl_str_mv Venturini, Tarcieli Pozzebon
contributor_str_mv Alves, Sydney Hartz
Fuentefria, Alexandre Meneghello
Lopes, Paulo Guilherme Markus
Trindade, Priscila de Arruda
dc.subject.por.fl_str_mv Suscetibilidade
Quimissensibilizantes
Associações
Antifúngicos
Sinergismo
Fusarium spp.
topic Suscetibilidade
Quimissensibilizantes
Associações
Antifúngicos
Sinergismo
Fusarium spp.
Susceptibility
Chemosensitizers
Associations
Antifungals
Synergism
CNPQ::CIENCIAS DA SAUDE::FARMACIA
dc.subject.eng.fl_str_mv Susceptibility
Chemosensitizers
Associations
Antifungals
Synergism
dc.subject.cnpq.fl_str_mv CNPQ::CIENCIAS DA SAUDE::FARMACIA
description The genus Fusarium is characterized by hyaline filamentous fungi that cause a wide spectrum of infections predominantly in immunocompromised patients. Disseminated fusariosis results in high rates of morbidity and mortality, since it is of difficult prevention and treatment. The remarkable primary resistance to conventional antifungals of this genus requires the search for new therapeutic possibilities. A possible attempt is the combination of antifungals and chemosensitizing agents with different mechanisms of action. This study aimed to evaluate the in vitro susceptibility of Fusarium to conventional antifungal agents (amphotericin B, itraconazole, voriconazole and caspofungin); organoselenium compounds (diphenyl diselenide and ebselen), nonantifungal drugs (amiodarone, doxycycline, moxifloxacin, pentamidine, polymyxin B, tigecycline and tobramycin), and phytocompounds (cinnamaldehyde, carvacrol and thymol), through broth microdilution method (M38-A2, CLSI). The combinations between the antifungal agents and chemosensitizers were assessed through the checkerboard technique. Among the antifungals tested amphotericin B showed greater activity in vitro (0.25-8 μg/ml); followed by voriconazole (1-16 μg/ml), itraconazole (>16 μg/ml) and caspofungin (>32 μg/ml). Diphenyl diselenide (4-32 μg/ml), ebselen (2-8 μg/ml), pentamidine (4-32 μg/ml) and polymyxin B (4-16 μg/ml) also showed antifungal activity against Fusarium spp. Ebselen and diphenyl diselenide presented high rates of synergism in combination with amphotericin B (88% and 72%, respectively) or voriconazole (80% e 64%, respectively). Combinations with nonantifungal drugs have also resulted in synergism, highlighting the following associations (% of synergism): tobramycin + amphotericin B (80%) or voriconazole (76%); polymyxin B + amphotericin B (76%) or voriconazole (64%); pentamidine + amphotericin B (72%) or voriconazole (68%); amiodarone + amphotericin B (64%) or voriconazole (76%); and moxifloxacin + amphotericin B (72%) or voriconazole (60%). Furthermore, the phytocompounds thymol and carvacrol have showed potent chemosensitizer activity in association to caspofungin (96% e 88%, respectively). Among all the tested combinations, no antagonistic interactions were observed. In conclusion, the most relevant combinations deserve a future investigation in vivo experimental models, since these associations suggest new potencial candidates for combined therapy against fusariosis.
publishDate 2016
dc.date.issued.fl_str_mv 2016-03-24
dc.date.accessioned.fl_str_mv 2019-08-29T20:38:52Z
dc.date.available.fl_str_mv 2019-08-29T20:38:52Z
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dc.publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências da Saúde
dc.publisher.program.fl_str_mv Programa de Pós-Graduação em Ciências Farmacêuticas
dc.publisher.initials.fl_str_mv UFSM
dc.publisher.country.fl_str_mv Brasil
dc.publisher.department.fl_str_mv Farmacologia
publisher.none.fl_str_mv Universidade Federal de Santa Maria
Centro de Ciências da Saúde
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repository.name.fl_str_mv Biblioteca Digital de Teses e Dissertações do UFSM - Universidade Federal de Santa Maria (UFSM)
repository.mail.fl_str_mv atendimento.sib@ufsm.br||tedebc@gmail.com
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