Autor(es)

Conde, Camila Aparecida da Silva Dos Reis ; Bruno, Katherine Lima ; Calcado, Camilla Barbosa ; Delgado, Giset Y. Sanchez ; Oliveira, Willian Xerxes Coelho ; Silva, Heveline ; Navarro, Maribel

• Tipo de documento: Artigo Científico
• Fonte: Journal of Inorganic Biochemistry; v. 275, p. 15-pg., 2026-02-01.

Resumo

According to the World Health Organization, an estimated 9.7 million people died from cancer worldwide in 2024. Considering this devastating scenario, our strategy is to search for gold(I) compounds with the potential to be used as anticancer drugs. We have synthesized the organometallic gold(I)-NHC methylclotrimazole (CTZMe, 1) and gold(I)-NHC methylketoconazole (KTZMe, 2), as well as the gold(I)-CTZ (clotrimazole)/KTZ (ketoconazole) coordination compounds (3-4). Their structures were confirmed through full characterization using analytical and spectroscopic techniques including elemental analysis, molar conductivity, infrared (IR), ultraviolet-visible (UV-Vis), magnetic nuclear resonance (NMR), electrospray ionization mass spectrometry (ESI-MS), and X-ray diffraction of a single crystal for complex 1, with additional support from theoretical calculations. Gold(I) complexes (1-4) were tested against tumor cell lines (MDA-MB-231 and 4 T1) and in a normal cell line (MCF-10 A), revealing that complexes 1-4 were generally more active and selective than free imidazole antifungal drugs and their imidazolium salts, with compound 1 being the most active. These gold complexes (1-4) were found to interact with DNA; however, this was not the main target. Instead, they displayed substantial interaction with glutathione, as determined by colorimetric assay and NMR-monitored analysis, suggesting preferential interaction with thiol-containing enzymes such as Thioredoxin Reductase (TrxR). Molecular docking suggested two possible modes of TrxR inhibition: (i) redox-center blockade by KTZ-containing compounds (2 and 4) and (ii) direct Au-S binding by CTZ-based compounds (1 and 3), particularly for the most active complex 1, which might contribute to its higher anticancer activity. (AU)

• Processo FAPESP: 13/07375-0 - CeMEAI - Centro de Ciências Matemáticas Aplicadas à Indústria
• Beneficiário: Francisco Louzada Neto
• Modalidade de apoio: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs