Novel echinocandin antifungals. Part 1: Novel side-chain analogs of the natural product FR901379

A series of novel acylated analogs of the novel water-soluble echinocandin FR901379 have been prepared and evaluated for antifungal and hemolytic activity. A relationship between antifungal activity and lipophilicity of the acyl side chain, expressed as Clog P was demonstrated, and an analog (3c) with 5.5- to 8-fold superior in vivo activity relative to the previously disclosed 4-(n-octyloxy)benzoyl side chain analog, FR131535 obtained.

Graphical abstractA series of novel acylated analogs of the novel water-soluble echinocandin FR901379 have been prepared. Compound 3c shows both potent antifungal activity and weak hemolytic activity.Figure optionsDownload full-size imageDownload as PowerPoint slide