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

Author(s)

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]}

Affiliation

^[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

• Document type: Review article
• Source: CURRENT TOPICS IN MEDICINAL CHEMISTRY; v. 18, n. 27, p. 2338-2346, 2018.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 15/17623-6 - Evaluation of the Leishmanicidal Potential from Drugs which Act in the Sterols Biochemical Pathway
• Grantee: Eduardo Seiji Yamamoto
• Support Opportunities: Scholarships in Brazil - Master
• FAPESP's process: 16/00468-0 - Use of drug repurposing and natural product bioprospection to characterize compounds with in vitro and in vivo leishmanicidal action
• Grantee: Luiz Felipe Domingues Passero
• Support Opportunities: Regular Research Grants