nystatin-a1 and fenticonazole

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.

Topics: Antiprotozoal Agents; Imidazoles; Leishmania; Nystatin; Parasitic Sensitivity Tests; Species Specificity

Various tests were used in order to ascertain any irritating, sensitising or toxic potential of alpha-(2,4-dichlorophenyl)-beta,N-imidazolylethyl 4-phenylthiobenzyl ether nitrate (fenticonazole, Rec 15/1476) when applied to the skin or to mucous membranes in gel or cream formulation. When instilled into the conjunctival sac in rabbits fenticonazole led to a slight reddening of the mucosa in only one animal. The reddening appeared 1 h after treatment and disappeared within 24 h. Guinea pigs topically treated for 20 days with fenticonazole 2% gel or cream showed mild erythema which appeared 5 days after the beginning of the treatment and virtually disappeared at the end of the treatment. The treatment with fenticonazole 2% gel or cream did not induce sensitisation. Fenticonazole was not phototoxic or photosensitising when a 2% gel or cream formulation was applied topically to guinea pigs, at the dosage of 0.1 ml per animal.

Topics: Administration, Topical; Animals; Conjunctivitis; Griseofulvin; Guinea Pigs; Imidazoles; Miconazole; Mucous Membrane; Nystatin; Photosensitivity Disorders; Rabbits; Skin