Synthesis, characterization and biological evaluation of zinc and copper azasterol complexes against Sporothrix brasiliensis

Abstract

New copper(I), copper(II) and zinc(II) azasterol derivatives were prepared using 20-hydrazone-imidazolin-2-yl-5α-pregnan-3β-ol (H1) as a ligand. The reactions were carried out under mild experimental conditions with different zinc(II) and copper(II) salts to produce [Zn(H1)₂(OH)₂] (1), [Zn(H1)₂Cl₂] (2), [Zn(H1)₃(NO₃)]NO₃ (3), [Cu(H1)₂(OH)₂] (4), [Cu(H1)₂]Cl (5) and [Cu(H1)₂]NO₃ (6). They were fully characterized by analytical and spectroscopic techniques. The molecular structure of these six metal complexes was also investigated by computational methods (DFT) to get information on the most stable geometry configuration around the metal atoms Zn and Cu. Antifungal activities of H1, compounds 1–6, and itraconazole (ITZ) as positive controls were tested in vitro against S. brasiliensis. The results showed that the fungus was more susceptible to all metal–azasterol complexes than H1. The most efficient metal–azasterol complex was [Zn(H1)₂(OH)₂] (1), with IC₅₀ equal to that of itraconazole (0.25 μM). These biological results demonstrated that metal–azasterol complexes are promising molecules in the search and development of new antifungal compounds.