Synthesis and Biological Activity of Novel Zinc-Itraconazole Complexes in Protozoan Parasites and Sporothrix spp

新型锌-伊曲康唑配合物的合成及其对原生动物寄生虫和孢子丝菌属的生物活性

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作者:Jose Aleixo de Azevedo-França, Renato Granado, Sara Teixeira de Macedo Silva, Gabrielle Dos Santos-Silva, Sandra Scapin, Luana P Borba-Santos, Sonia Rozental, Wanderley de Souza, Érica S Martins-Duarte, Emile Barrias, Juliany Cola Fernandes Rodrigues, Maribel Navarro

Abstract

The new complexes Zn(ITZ)2Cl2 (1) and Zn(ITZ)2(OH)2 (2) were synthetized by a reaction of itraconazole with their respective zinc salts under reflux. These Zn-ITZ complexes were characterized by elemental analyses, molar conductivity, mass spectrometry, 1H and 13C{1H} nuclear magnetic resonance, and UV-vis and infrared spectroscopies. The antiparasitic and antifungal activity of Zn-ITZ complexes was evaluated against three protozoans of medical importance, namely, Leishmania amazonensis, Trypanosoma cruzi, and Toxoplasma gondii, and two fungi, namely, Sporothrix brasiliensis and Sporothrix schenckii The Zn-ITZ complexes exhibited a broad spectrum of action, with antiparasitic and antifungal activity in low concentrations. The strategy of combining zinc with ITZ was efficient to enhance ITZ activity since Zn-ITZ-complexes were more active than the azole alone. This study opens perspectives for future applications of these Zn-ITZ complexes in the treatment of parasitic diseases and sporotrichosis.

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