In vitro and in silico antileishmania activity of voriconazole (Vfend)
Atividade antileishmania in vitro e in silico do voriconazol (Vfend)
Palavras-chave:
Leishmania, Molecular modeling, PromastigotesResumo
American Cutaneous Leishmaniasis (ACL) is a public health problem in 88 countries. The treatment of ATL is based on pentavalent antimony, which has several adverse effects. And through new alternatives for the treatment of leishmaniasis, the use of off-label medications appears. The objective of this work was to evaluate, through in vitro and in silico tests, the activity of voriconazole in tablet form as off-label against the promastigote forms of Leishmania amazonensis and Leishmania guyanensis. In the bioassay, species of Leishmania (L.) amazonensis and Leishmania (V.) guyanensis were used, cultivated in RPMI medium with 10% SFBi. The 50% inhibitory concentration (IC50) of voriconazole was evaluated by the inhibition of promastigotes exposed to voriconazole at concentrations of 6.25 to 200 µg.mL-1 diluted in culture medium and fluconazole at 25 to 400 µg.mL-1. In the experiment, parasites plus culture medium and pentamidine isethionate at 3 µg.mL-1 were used as controls for 24, 48 and 72 h in triplicate. The concentrations of voriconazole used in the test showed antileishmanial activity against promastigotes of both Leishmania species, with an IC50 of 5.34 µg.mL-1 for L. amazonensis and 5.66 µg.mL-1 for L. guyanensis. Therefore, the study showed that off-label voriconazole presented better results than fluconazole against Leishmania species, in addition to showing better enzymatic coupling of new targets.
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