New Antifungal Agents with Azole Moieties

Fungal conditions affect a multitude of people worldwide, leading to increased hospitalization and mortality rates, and the need for novel antifungals is emerging with the rise of resistance and immunocompromised patients. Continuous use of azole drugs, which act by inhibiting the fungal CYP51, involved in the synthesis of ergosterol, essential to the fungal cell membrane, has enhanced the resistance and tolerance of some fungal strains to treatment, thereby limiting the arsenal of available drugs. The goal of this review is to gather literature information on new promising azole developments in clinical trials, with in vitro and in vivo results against fungal strains, and complementary assays, such as toxicity, susceptibility assays, docking studies, among others. Several molecules are reviewed as novel azole structures in clinical trials and with recent/imminent approvals, as well as other innovative molecules with promising antifungal activity. Structure-activity relationship (SAR) studies are displayed whenever possible. The azole moiety is brought over as a privileged structure, with multiple different compounds emerging with distinct pharmacophores and SAR. Particularly, 1,2,3-triazole natural product conjugates emerged in the last years, presenting promising antifungal activity and a broad spectrum against various fungi.