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

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]}

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

• 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
• Modalidade de apoio: 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
• Modalidade de apoio: Auxílio à Pesquisa - Regular