Exploring novel copper(II) binding azole compounds as potential antifungal drugs

"Invasive fungal infections are a major cause of morbidity and mortality among hospitalized patients and immunocompromised individuals. The increasing resistance of pathogenic fungi to the limited number of antifungal classes available makes the development of new and improved antifungals a pressing issue. This work aims to synthesize new azole compounds by molecular simplification of the model antifungal drug fluconazole while incorporating chemical functions that bind copper(II), to explore a potential synergy between the azoles and the metal. The target compounds designed are based on a central amine functionalized with three functions: an azole, a dihalogenobenzyl, and a varying copper(II) binding function. The 15 target compounds synthesized are organized in three families, which differ on the azole used (triazole or imidazole) and the length of the alkyl chain separating the central amine and the azole. Differences within each family are the copper(II) binding function used and, in one case, also the dihalogenobenzyl moiety. Such structural variations are expected to allow for a structure-activity relationship study based on the results of biological activity assays performed.(...)