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© A. Alanio, E. Perret
Prolifération de Cryptococcus neoformans dans des macrophages murins.
Publication : Antimicrobial agents and chemotherapy

and Efficacy of a Novel and Long-Acting Fungicidal Azole, PC1244, on Aspergillus fumigatus Infection

Scientific Fields
Diseases
Organisms
Applications
Technique

Published in Antimicrobial agents and chemotherapy - 26 Apr 2018

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

Link to Pubmed [PMID] – 29439966

Antimicrob. Agents Chemother. 2018 05;62(5)

The antifungal effects of the novel triazole PC1244, designed for topical or inhaled administration, against were tested in a range of and studies. PC1244 demonstrated potent antifungal activities against clinical isolates ( = 96) with a MIC range of 0.016 to 0.25 μg/ml, whereas the MIC range for voriconazole was 0.25 to 0.5 μg/ml. PC1244 was a strong tight-binding inhibitor of recombinant CYP51A and CYP51B (sterol 14α-demethylase) enzymes and strongly inhibited ergosterol synthesis in with a 50% inhibitory concentration of 8 nM. PC1244 was effective against a broad spectrum of pathogenic fungi (MIC range, <0.0078 to 2 μg/ml), especially , , , , , , , and PC1244 also proved to be quickly absorbed into both hyphae and bronchial epithelial cells, producing persistent antifungal effects. In addition, PC1244 showed fungicidal activity (minimum fungicidal concentration, 2 μg/ml) which indicated that it was 8-fold more potent than voriconazole. , once-daily intranasal administration of PC1244 (3.2 to 80 μg/ml) to temporarily neutropenic, immunocompromised mice 24 h after inoculation with itraconazole-susceptible substantially reduced the fungal load in the lung, the galactomannan concentration in serum, and circulating inflammatory cytokine levels. Furthermore, 7 days of extended prophylaxis with PC1244 showed effects superior to those of 1 day of prophylactic treatment, suggesting accumulation of the effects of PC1244. Thus, PC1244 has the potential to be a novel therapy for the treatment of infection in the lungs of humans.

https://www.ncbi.nlm.nih.gov/pubmed/29439966