Synthesis, characterization and biological evaluation of zinc and copper azasterol complexes against <i>Sporothrix brasiliensis</i>

Justo, Rodrigo M. S.; Borba-Santos, Luana Pereira; Sade, Youssef Bacila; Ferreira, Frederico Henrique C.; Rosa, Nathália M. P.; Costa, Luiz Antônio S.; Visbal, Gonzalo; Rozental, Sônia; Navarro, Maribel

doi:10.1039/d1nj03656d

Cited by 2 publications

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“…In addition, the incorporation of bioactive ligands to zinc to obtain drugs with biological activity towards parasitic infections, such as Leishmaniasis, Chagas disease, and Sporothrix sp., have been reported in the literature [5,18,20,27]. A recent work developed by our group, which shows the use of trace metals in association with azasterol derivatives, described the synthesis of copper and zinc-azasterol complexes and their antifungal activity against Sporothrix brasiliensis [31]. However, the use of zincazasterol complexes as anti-Leishmania agents has yet to be reported; therefore, our interest is to provide the synthesis and characterization of a new ZnCl 2 (H3) 2 , or also called here ZnH3 complex, as well as its biological activity against Leishmania amazonensis [32].…”

Section: Introductionmentioning

confidence: 99%

Zinc(II)-Sterol Hydrazone Complex as a Potent Anti-Leishmania Agent: Synthesis, Characterization, and Insight into Its Mechanism of Antiparasitic Action

et al. 2023

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Searching for new alternatives for treating leishmaniasis, we present the synthesis, characterization, and biological evaluation against Leishmania amazonensis of the new ZnCl2(H3)2 complex. H3 is 22-hydrazone-imidazoline-2-yl-chol-5-ene-3β-ol, a well-known bioactive molecule functioning as a sterol Δ24-sterol methyl transferase (24-SMT) inhibitor. The ZnCl2(H3)2 complex was characterized by infrared, UV-vis, molar conductance measurements, elemental analysis, mass spectrometry, and NMR experiments. The biological results showed that the free ligand H3 and ZnCl2(H3)2 significantly inhibited the growth of promastigotes and intracellular amastigotes. The IC50 values found for H3 and ZnCl2(H3)2 were 5.2 µM and 2.5 µM for promastigotes, and 543 nM and 32 nM for intracellular amastigotes, respectively. Thus, the ZnCl2(H3)2 complex proved to be seventeen times more potent than the free ligand H3 against the intracellular amastigote, the clinically relevant stage. Furthermore, cytotoxicity assays and determination of selectivity index (SI) revealed that ZnCl2(H3)2 (CC50 = 5 μΜ, SI = 156) is more selective than H3 (CC50 = 10 μΜ, SI = 20). Furthermore, as H3 is a specific inhibitor of the 24-SMT, free sterol analysis was performed. The results showed that H3 was not only able to induce depletion of endogenous parasite sterols (episterol and 5-dehydroepisterol) and their replacement by 24-desalkyl sterols (cholesta-5,7,24-trien-3β-ol and cholesta-7,24-dien-3β-ol) but also its zinc derivative resulting in a loss of cell viability. Using electron microscopy, studies on the fine ultrastructure of the parasites showed significant differences between the control cells and parasites treated with H3 and ZnCl2(H3)2. The inhibitors induced membrane wrinkle, mitochondrial injury, and abnormal chromatin condensation changes that are more intense in the cells treated with ZnCl2(H3)2.

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Section: Introductionmentioning

confidence: 99%

Zinc(II)-Sterol Hydrazone Complex as a Potent Anti-Leishmania Agent: Synthesis, Characterization, and Insight into Its Mechanism of Antiparasitic Action

et al. 2023

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Biosynthesis of ergosterol as a relevant molecular target of metal-based antiparasitic and antifungal compounds

Scalese,

Mosquillo,

Pérez-Díaz

et al. 2024

Coordination Chemistry Reviews

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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 ligand. The reactions were carried out under mild experimental conditions with different Zinc(II) and Copper(II) salts to...

Cited by 2 publications

References 44 publications

Zinc(II)-Sterol Hydrazone Complex as a Potent Anti-Leishmania Agent: Synthesis, Characterization, and Insight into Its Mechanism of Antiparasitic Action

Zinc(II)-Sterol Hydrazone Complex as a Potent Anti-Leishmania Agent: Synthesis, Characterization, and Insight into Its Mechanism of Antiparasitic Action

Biosynthesis of ergosterol as a relevant molecular target of metal-based antiparasitic and antifungal compounds

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