Posaconazole [171228-49-2]

Biological Activity

Posaconazole (trade name Noxafil) is a sterol C14α demethylase inhibitor with IC50 of 0.25 nM. Posaconazole blocks the synthesis of ergosterol by inhibiting of the enzyme lanosterol 14α-demethylase and accumulation of methylated sterol precursors. Posaconazole disrupts the close packing of acyl chains of phospholipids and impairs the functions of certain membrane-bound enzyme systems such as ATPase and enzymes of the electron transport system, thus inhibiting growth of the fungi. Posaconazole is significantly more potent at inhibiting 14-alpha demethylase than itraconazole. Oral administration of posaconazole taken with a high-fat meal exceeds 90% bioavailability and increases the concentration by four times compared to fasting state. Posaconazole is currently in a phase 2 clinical trial in Argentina testing its efficacy against asymptomatic, chronic Chagas.

Chemical Information

Molecular Weight	700.78
Formula	C37H42F2N8O4
CAS Number	171228-49-2
Solubility (25°C)	DMSO 100 mg/mL
Storage	Powder          -20°C   3 years ;  4°C   2 years In solvent       -80°C   6 months ;  -20°C   1 month

References

[1] Veiga-Santos P, et al. Int J Antimicrob Agents. Effects of amiodarone and posaconazole on the growth and ultrastructure of Trypanosoma cruzi.

[2] Sabatelli F, et al. Antimicrob Agents Chemother. In vitro activities of posaconazole, fluconazole, itraconazole, voriconazole, and amphotericin B against a large collection of clinically important molds and yeasts.

[3] Benaim G, et al. J Med Chem. Amiodarone has intrinsic anti-Trypanosoma cruzi activity and acts synergistically with posaconazole.