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From Proteopedia

Revision as of 20:49, 28 March 2017

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Introduction

Noxafil, also known as Posaconazole, is an antifungal drug used to treat fungal infections caused by Candida and Aspergillus species, as well as treat other fungal infections such as chromoblastomycosis, mycetoma, and coccidioidomycosis. Noxafil is also often used when other antifungal medicines are tolerated or if the patient is immunocompromised. Noxafil is under the triazole class of antifungal drugs and works by inhibiting the production of ergosterol, an important factor in fungi cell membranes, leading to prevention of cell growth and ultimately death.

Structure

• Chemical Formula: C37H42F2N8O4
• Molecular Weight: 700.792 g/mol
• IUPAC name: 4-[4-[4-[4-[[(3R,5R)-5-(2,4-difluorophenyl)-5-(1,2,4-triazol-1-ylmethyl)oxolan-3-yl]methoxy]phenyl]piperazin-1-yl]phenyl]-2-[(2S,3S)-2-hydroxypentan-3-yl]-1,2,4-triazol-3-one

Function

Relevance

Mechanism

spinqualitylabelsall models Crystal structure of sterol 14-alpha demethylase (CYP51) from a pathogenic yeast Candida albicans in complex with the antifungal drug posaconazole Show:Asymmetric Unit Biological Assembly Drag the structure with the mouse to rotate   Export Animated Image

When administered, Posaconazole acts as an antifungal by blocking Lanosterol 14α-demethylase, a P-450 dependant fungal enzyme containing heme as a cofactor. Posaconazole binds to the heme cofactor that the enzyme contains, which prevents the fungus from creating ergosterol, an essential component of the fungal cell membrane. Ergosterol performs in fungal cells how cholesterol does in animal cells, making the cell membrane less permeable. Without it, the cells can no longer proliferate and eventually die because the cell membranes become “leaky”, releasing essential organic components from the cell’s interior and preventing it from performing normal cellular functions. In this way, Posaconazole acts both as fungicidal and fungistatic.

Pharmacology

References

PCID: 468595 http://www.ema.europa.eu/ema/index.jsp?curl=pages/medicines/human/medicines/000610/human_med_000937.jsp&mid=WC0b01ac058001d124 http://www.tandfonline.com/doi/full/10.1586/14787210.3.4.467