A novel polyaminocarboxylate compound to treat murine pulmonary aspergillosis by interfering with zinc metabolism.

A novel polyaminocarboxylate compound to treat murine pulmonary aspergillosis by interfering with zinc metabolism. Antimicrob Agents Chemother. 2018 Apr 09;: Authors: Laskaris P, Vicentefranqueira R, Helynck O, Jouvion G, Calera JA, du Merle L, Suzenet F, Buron F, Alves de Sousa R, Mansuy D, Cavaillon JM, Latgé JP, Munier-Lehmann H, Ibrahim-Granet O Abstract Aspergillus fumigatus can cause pulmonary aspergillosis in immunocompromised patients and is associated with a high mortality rate due to the lack of reliable treatment options. This opportunistic pathogen requires zinc in order to grow and cause disease. Novel compounds that interfere with fungal zinc metabolism may therefore be of therapeutic interest. We screened chemical libraries containing 59223 small molecules using a resazurin assay that compared their effects on an A. fumigatus wild type strain grown under zinc-limiting conditions and on a zinc transporter knockout strain grown under zinc-replete conditions to identify compounds affecting zinc metabolism. After a first screen 116 molecules were selected whose inhibitory effect on fungal growth was further tested by using luminescence assays and hyphal length measurements to confirm their activity, as well as to toxicity assays on HeLa cells and mice. Six compounds were selected following a re-screening, two of which were pyrazolones, two were porphyrins and two were polyaminocarboxylates. All three groups showed good in...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research