Current Status and Structure Activity Relationship of Privileged Azoles as Antifungal Agents (2016-2020)

Fungal infections have greatly contributed to infectious-related deaths in the past century. This issue has become worse with the advent of immunity-impairing conditions such as HIV. The eukaryote nature of fungal pathogens makes them harder to eradicate than bacterial infections. Given the importance of the problem, considerable efforts have been made to the synthesis and biological assessment of azole-based chemical scaffolds and their bioisosteres. The emergence of validated macromolecular targets within different fungal species has inspired structure-based drug design strategies toward diverse azole-based agents. Despite advantageous features, the emergence of drug-resistant fungal species has restricted the applicability of current azoles as first-line antifungal agents. Consequently, it appears advisable to elucidate the structure activity relationships (SAR) and chemical biodiversity within antifungal azoles. This review is devoted to a brief look at clinically applied drugs, structure-based classification of azole antifungals and their SAR. The reviewed molecules belong to the antifungal structures that were reported throughout 2016-2020.(c) 2022 Elsevier Ltd and International Society of Antimicrobial Chemotherapy. All rights reserved.

Automated summary

Fungal infections have been a major cause of infectious-related deaths, especially with the rise of immune-compromising conditions like HIV. Fungal pathogens, being eukaryotes, are more difficult to eliminate compared to bacterial infections. Research on the structure-activity relationships and chemical diversity of antifungal azoles is important for combating drug-resistant fungal species.