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Curr Top Med Chem. 2018;18(27):2338-2346. doi: 10.2174/1568026619666181220114627.

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

Author information

1
Laboratory of Pathology of Infectious Diseases (LIM50), Department of Pathology, Medical School of Sao Paulo University, Av. Dr. Arnaldo, 455. Cerqueira Cesar, Sao Paulo, 01246-903, SP, Brazil.
2
Sao Paulo State University (UNESP), Institute of Biosciences, Sao Vicente, Praca Infante Dom Henrique, s/n, 11330-900 Sao Vicente, SP, Brazil.
3
Pathology Department, Case Western Reserve University, 2103 Cornell Rd, Room 5503, Cleveland, OH 44106, United States.
4
Sao Paulo State University (UNESP), Institute for Advanced Studies of Ocean, Sao Vicente. Av. Joao Francisco Bensdorp, 1178, 11350-011 São Vicente, SP, Brazil.

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.

KEYWORDS:

Anti-fungal drugs; Anti-hyperlipidemic drugs; Drug repurposing; Fenticonazole; New World Leishmaniasis; Nystatin; Tioconazole.

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