In Vitro and In Vivo Efficacy of a Novel and Long Acting Fungicidal Azole, PC1244 on Aspergillus fumigatus Infection.

In Vitro and In Vivo Efficacy of a Novel and Long Acting Fungicidal Azole, PC1244 on Aspergillus fumigatus Infection. Antimicrob Agents Chemother. 2018 Feb 12;: Authors: Colley T, Sehra G, Chowdhary A, Alanio A, Kelly SL, Kizawa Y, Armstrong-James D, Fisher MC, Warrilow AGS, Parker JE, Kelly DE, Kimura G, Nishimoto Y, Sunose M, Onions S, Crepin D, Lagasse F, Crittall M, Shannon J, McConville M, King-Underwood J, Naylor A, Bretagne S, Murray J, Ito K, Strong P, Rapeport G Abstract The antifungal effects of the novel triazole, PC1244, designed for topical or inhaled administration, against A. fumigatus have been tested in a range of in vitro and in vivo studies. PC1244 demonstrated potent antifungal activities against clinical A. fumigatus isolates (N=96) with a MIC range of 0.016--0.25 μg/ml, whereas the MIC range for voriconazole was 0.25--0.5 μg/ml. PC1244 was a strong tight-binding inhibitor of recombinant A. fumigatus CYP51A and CYP51B (sterol 14α-demethylase) enzymes and strongly inhibited ergosterol synthesis in A. fumigatus with an IC50 of 8 nM. PC1244 was effective against a broad spectrum of pathogenic fungi (MIC ranged from <0.0078∼2 μg/ml), especially on Aspergillus terreus, Trichophyton rubrum, Candida albicans, Candida glabrata, Candida krusei, Cryptococcus gattii, Cryptococcus neoformans and Rhizopus oryzae PC1244 also proved to be quickly absorbed into both A. fumigatus hyphae and bronchial epithelial cells, pr...
Source: Antimicrobial Agents and Chemotherapy - Category: Microbiology Authors: Tags: Antimicrob Agents Chemother Source Type: research