Synthesis of New Azoles For the Treatment of Resistant Infections Caused By Who Critical Priority Fungi: Therapeutic Challenges and Innovations in The Fight Against Them

Objective: The study aimed to conduct a review of new azoles derivatives to tackle the critical priority pathogens of the World Health Organization (WHO). Theoretical background: Azoles are the main class of antifungal drugs, and the creation of new drugs based on their fundamental structure could be a viable alternative for combating pathogens listed by the WHO as critical due to their high mortality and resistance. Method: The review used databases such as PubMed, Scopus and Science Direct, with articles published between 2019 and 2024. Papers addressing infections caused by these fungi and azole derivatives as an alternative against priority pathogens were included, and 20 articles were selected. Results and discussion: The WHO list highlights the pathogens Candida albicans, Cryptococcus neoformans, Aspergillus fumigatus and Candida auris, which are in urgent need of new therapeutic alternatives. Experimental studies have revealed significant advances in the structural modification of azoles, especially in relation to hybrid compounds combining triazole and oxadiazole nuclei and triazole derivatives containing hydrophobic substituents, which have a broad spectrum and mechanisms of action. Research implications: Resistance to antifungal drugs has increased globally and threatens the effectiveness of available treatments. The synthesis of new azoles derivatives can help fill therapeutic gaps, these modifications can serve as a basis for the development of new drugs with improved mechanisms of action. Originality and value: Novel structural modifications to azole molecules, such as the combination of triazole and oxadiazole cores, and the introduction of hydrophobic groups, which not only increase efficacy, but also improve penetration into biofilms and thermal stability. These innovations represent a significant advance for the treatment of fungal pathogens in need of new therapies.