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(Referência obtida automaticamente do Web of Science, por meio da informação sobre o financiamento pela FAPESP e o número do processo correspondente, incluída na publicação pelos autores.)

Activity of Fenticonazole, Tioconazole and Nystatin on New World Leishmania Species

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Autor(es):
Yamamoto, Eduardo Seiji [1] ; Jesus, Jessica Adriana [1] ; Bezerra-Souza, Adriana [2] ; Laurenti, Marcia Dalastra [1] ; Ribeiro, Susan Pereira [3] ; Domingues Passero, Luiz Felipe [2, 4]
Número total de Autores: 6
Afiliação do(s) autor(es):
[1] Univ Sao Paulo, Med Sch, Dept Pathol, Lab Pathol Infect Dis LIM50, Av Dr Arnaldo 455, BR-01246903 Sao Paulo, SP - Brazil
[2] Sao Paulo State Univ UNESP, Inst Biosci, Praca Infante Dom Henrique S-N, BR-11330900 Sao Vicente, SP - Brazil
[3] Case Western Reserve Univ, Pathol Dept, 2103 Cornell Rd, Room 5503, Cleveland, OH 44106 - USA
[4] Sao Paulo State Univ UNESP, Inst Adv Studies Ocean, Av Joao Francisco Bensdorp 1178, BR-11350011 Sao Vicente, SP - Brazil
Número total de Afiliações: 4
Tipo de documento: Artigo de Revisão
Fonte: CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. 18, n. 27, p. 2338-2346, 2018.
Citações Web of Science: 1
Resumo

Leishmaniasis is an infectious disease caused by protozoal parasites belonging to Leishmania genus. Different clinical outcomes can be observed depending on the parasite species and health condition of patients. It can range from single cutaneous lesion until deadly visceral form. The treatment of all forms of leishmaniasis is based on pentavalent antimonials, and in some cases, the second-line drug, amphotericin B is used. Beside the toxicity of both drugs, parasites can be resistant to antimonial in some areas of the world. This makes fundamental the characterization of new drugs with leishmanicidal effect. Thus, the aim of the present work was to study the leishmanicidal activity of drugs able to interfere with ergosterol pathway (fenticonazole, tioconazole, nystatin, rosuvastatin and voriconazole) against promastigote and amastigote forms of L.(L.) amazonensis, L.(V.) braziliensis and L.(L.) infantum, and its impact on morphological and physiological changes in L.(L.) amazonensis or in host macrophages. We observed that fenticonazole, tioconazole and nystatin drugs eliminated promastigote and intracellular amastigotes, being fenticonazole and nystatin the most selective towards amastigote forms. Rosuvastatin and voriconazole did not present activity against amastigote forms of Leishmania sp. In addition, the drugs with leishmanicidal activity interfered with parasite mitochondrion. Although drugs did not stimulate NO and H2O2, specially fenticonazole was able to alkalize infected host macrophages. These results suggest well established and non-toxic antifungal drugs can be repurposed and used in leishmaniasis. (AU)

Processo FAPESP: 15/17623-6 - Avaliação do potencial leishmanicida de fármacos que atuam na rota bioquímica de esteróis
Beneficiário:Eduardo Seiji Yamamoto
Linha de fomento: Bolsas no Brasil - Mestrado
Processo FAPESP: 16/00468-0 - Uso do reposicionamento de fármacos e da bioprospecção de produtos naturais para caracterizar compostos com ação leishmanicida in vitro e in vivo
Beneficiário:Luiz Felipe Domingues Passero
Linha de fomento: Auxílio à Pesquisa - Regular