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

• Published in: International journal of antimicrobial agents 2022-03, Vol.59 (3), p.106518-106518, Article 106518
• Main Authors: Ahmadi, A., Mohammadnejadi, E., Karami, P., Razzaghi-Asl, N.
• Format: Article
• Language: English
• Subjects: Antifungal Agents - chemistry; Antifungal Agents - pharmacology; Azole; Azoles - pharmacology; Chemotherapy; Drug Resistance, Fungal; Fungal infection; Humans; Microbial Sensitivity Tests; Mycoses - drug therapy; Structure activity relationship
• ISSN: 0924-8579; 1872-7913
• DOI: 10.1016/j.ijantimicag.2022.106518

•Azoles significantly contribute to the chemotherapy of fungal infections.•The structure activity relationships of azole antifungals are discussed with regard to their chemical classification.•The selective effect against fungal species can be affected by structural polarity.•Few agents, such as biphenyl imidazoles, indicate regioselective/stereoselective action.•Several azole-based drug analogues are potent against azole-resistant fungal species. 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. [Display omitted]