Design, Synthesis and Antifungal Evaluation of Novel Pyrylium Salt In Vitro and In Vivo.

Nowadays, discovering new skeleton antifungal drugs is the direct way to address clinical fungal infections. Pyrylium salt was screened from a library containing 50,240 small molecules. Several studies about the antifungal activity and mechanism of have been reported, but the structure-activity relationship of pyrylium salts was not clear. To explore the chemical space of antifungal pyrylium salt , a series of pyrylium salt derivatives were designed and synthesized. Their antifungal activity and structure-activity relationships (SAR) were investigated. Compared with , most of the synthesized compounds exhibited equivalent or improved antifungal activities against in vitro. The synthesized compounds, such as , , , and exhibited comparable antifungal activities against with MIC values ranging from 0.47 to 1.0 μM. Fortunately, a compound numbered showed stronger antifungal activities and lower cytotoxicity was obtained. The MIC of compound against was 0.24 μM, and the cytotoxicity decreased 20-fold as compared to . In addition, was effective against fluconazole-resistant and other pathogenic species. More importantly, could significantly increase the survival rate of mice with a systemic infection, which suggested the good antifungal activities of in vitro and in vivo. Our results indicated that structural modification of pyrylium salts could lead to the discovery of new antifungal drugs.