Identification and characterization of a novel family of selective antifungal compounds (CANBEFs) which interfere with fungal protein synthesis.

Identification and characterization of a novel family of selective antifungal compounds (CANBEFs) which interfere with fungal protein synthesis. Antimicrob Agents Chemother. 2015 Jul 6; Authors: Mircus G, Albert N, Ben Yaakov D, Chikvashvili D, Shadkchan Y, Kontoyiannis DP, Osherov N Abstract Invasive mycotic infections have become more common during the last decades, posing an increasing threat to public health. However, despite the growing needs, treatments for invasive fungal infections remain unsatisfactory and are limited to a small number of antifungals. The aim of this study was to identify novel fungal cell-wall inhibitors from a library of small chemical compounds using a conditional protein kinase C (PKC) - expressing strain of Aspergillus nidulans sensitive to cell-wall-active agents. Eight 'hit' compounds affecting cell-wall integrity were identified from a screen of 35,000 small chemical compounds. Five shared a common basic molecular structure of 4-chloro-6-arylamino-7-nitro-benzofurazane (CANBEFs). The most potent compound, CANBEF-24, was further characterized and shown to inhibit growth of pathogenic Aspergillus, Candida, Fusarium and Rhizopus isolates at micromolar concentrations, while not affecting the growth of mammalian cell lines. CANBEF-24 demonstrated strong synergy in combination with caspofungin, an antifungal which inhibits cell-wall biosynthesis. Genetic and biochemical analyses in A. nidulans and Saccharo...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research