Cell lines

25 strains of Coccidioides immitis

Preparation method

The solubility of this compound in DMSO is >10 mM. General tips for obtaining a higher concentration: Please warm the tube at 37 ℃ for 10 minutes and/or shake it in the ultrasonic bath for a while.Stock solution can be stored below -20℃ for several months.

Reaction Conditions

MIC: 0.5 μg/ml, 48 hours

Applications

Posaconazole was tested in RPMI 1640 with L-glutamine and morpholinepropanesulfonic acid buffer at a concentration of 165 mM. The final concentration of the drug was 0.015 to 8 μg/ml. The MICs were read at 24 and 48 h. The posaconazole MICs ranged from 0.25 to 1 μg/ml, and the geometric mean posaconazole MIC was 0.5 μg/ml. The posaconazole MICs at which 50 of the isolates tested were inhibited (MIC50) and the MIC90 were 0.5 and 1 μg/ml, respectively.

Animal models

Male BALB/c mice

Dosage form

Oral administration, 5, 15, or 30 mg/kg twice per day, for 7 days

Applications

Mice were rendered neutropenic with single doses of 5-fluorouracil and with cyclophosphamide one day before infection. This treatment reduced the neutrophil count. Mice were infected intravenously using a 0.2-ml volume of the inoculums. The antifungal agent treatment began 1 day after infection. The survival of posaconazole recipients increased significantly in a dose-dependent manner over that of the controls, with 60 to 83% survival at the 30-mg/kg twice-daily dose. Posaconazole doses of 15 and 30 mg/kg significantly lowered counts in tissue. Posaconazole at a dose of 30 mg/kg reduced many counts to undetectable levels.

Other notes

Please test the solubility of all compounds indoor, and the actual solubility may slightly differ with the theoretical value. This is caused by an experimental system error and it is normal.

Posaconazole, also known as SCH 56592 or Noxafil, is a novel triazole antifungal compound that potently inhibits 14α-demethylation in a variety of fungi, including Candida (C. albicans C43, C. albicans C288, C. albicans C600 and C. albicans C248) and Aspergillus (A. fumigatus ND158 and A. flavus ND134), with half maximal inhibition concentration IC50 of 0.007 μg/ml, 0.06 μg/ml, 0.2 μg/ml, 0.3 μg/ml, 0.03 μg/ml and 0.03 μg/ml respectively [1].

Posaconzole, an itraconzole derivative with fluorine replacing chlorine in the phenyl ring and hydroxylation in the side chain, binds to the heme cofactor on the active site of 14α-demethylase, which converts lanosterol to 14α-dimethy lanosterol, resulting in the disruption of the integrity and function of the fungal cell membrane and inhibition of fungal growth [2].

References:
[1] Hanan K. Munayyer, Paul A. Mann, Andrew S. Chau, Taisa Yarosh-Tomaine, Jonathan R. Greene, Roberta S. Hare, Larry Heimark, Robert E. Palermo, David Loebenberg and Paul M. McNicholas. Posaconazole is a potent inhibitor of sterol 14α-demethylation in yeasts and molds. ANTIMICROBIAL AGENTS AND CHEMOTHERAPY. 2004; 48(10): 3690-3696
[2] Daryl S. Schiller and Horatio B. Fung. Posaconazole: an extended-spectrum triazole antifungal agent. Clinical Therapeutics. 2007; 29(9): 1862-1886