Posaconazole is a potent inhibitor of sterol 14alpha-demethylation in yeasts and molds

Antimicrobial Agents and Chemotherapy
Hanan K MunayyerPaul M McNicholas

Abstract

Posaconazole (POS; SCH 56592) is a novel triazole that is active against a wide variety of fungi, including fluconazole-resistant Candida albicans isolates and fungi that are inherently less susceptible to approved azoles, such as Candida glabrata. In this study, we compared the effects of POS, itraconazole (ITZ), fluconazole (FLZ), and voriconazole (VOR) on sterol biosynthesis in strains of C. albicans (both azole-sensitive and azole-resistant strains), C. glabrata, Aspergillus fumigatus, and Aspergillus flavus. Following exposure to azoles, nonsaponifiable sterols were extracted and resolved by liquid chromatography and sterol identity was confirmed by mass spectroscopy. Ergosterol was the major sterol in all but one of the strains; C. glabrata strain C110 synthesized an unusual sterol in place of ergosterol. Exposure to POS led to a decrease in the total sterol content of all the strains tested. The decrease was accompanied by the accumulation of 14alpha-methylated sterols, supporting the contention that POS inhibits the cytochrome P450 14alpha-demethylase enzyme. The degree of sterol inhibition was dependent on both dose and the susceptibility of the strain tested. POS retained activity against C. albicans isolates with mut...Continue Reading

References

Jan 1, 1987·Critical Reviews in Microbiology·H Vanden BosscheP Marichal
Sep 17, 1998·The Journal of Antimicrobial Chemotherapy·L W KitchenS P Day
Aug 25, 1999·The Journal of Antimicrobial Chemotherapy·A KoulM Ghannoum
Oct 30, 1999·Antimicrobial Agents and Chemotherapy·P MarichalH Vanden Bossche
Feb 15, 2001·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·S J LinS M Teutsch
Oct 16, 2001·Antimicrobial Agents and Chemotherapy·H NakayamaY Aoki
Aug 13, 2003·The Pediatric Infectious Disease Journal·Hilmar WisplinghoffMichael B Edmond

❮ Previous
Next ❯

Citations

May 17, 2006·Medical Mycology·G M AnsteadJ R Graybill
Jan 15, 2008·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Vijayalakshmi Nagappan, Stan Deresinski
Jan 22, 2005·Current Opinion in Pediatrics·Charalampos Antachopoulos, Thomas J Walsh
Sep 13, 2006·Antimicrobial Agents and Chemotherapy·Andrew S ChauPaul A Mann
Aug 30, 2005·Antimicrobial Agents and Chemotherapy·Andrew S ChauPaul M McNicholas
Feb 1, 2008·Journal of Clinical Microbiology·Guillermo Garcia-EffronDavid S Perlin
Jan 1, 2010·Infection and Drug Resistance·Voichita IanasStephen A Klotz
Jul 31, 2007·Future Microbiology·Fedja FarowskiOliver A Cornely
Jul 31, 2007·Future Microbiology·Jose A Vazquez
Mar 4, 2009·Expert Review of Anti-infective Therapy·Winter J SmithJohn R Perfect
Aug 19, 2005·Expert Review of Anti-infective Therapy·Andreas H Groll, Thomas J Walsh
Nov 19, 2010·Expert Review of Hematology·Aneesh K Mehta, Amelia A Langston
May 23, 2007·Expert Opinion on Pharmacotherapy·Douglas S Kwon, Eleftherios Mylonakis
Nov 20, 2012·European Journal of Medicinal Chemistry·Isabella P FerreiraJosé D Ardisson
Jan 8, 2016·Infectious Disease Clinics of North America·Jeniel E Nett, David R Andes
Feb 3, 2007·Médecine et maladies infectieuses·A Paugam
Oct 19, 2006·International Journal of Antimicrobial Agents·María Dolores Navarro-MartínezJosé Neptuno Rodríguez-López
Feb 12, 2009·Mycoses·Suganthini KrishnanPranatharthi H Chandrasekar
Aug 18, 2012·Diagnostic Microbiology and Infectious Disease·S Krishnan NatesanP H Chandrasekar
Jul 16, 2008·Journal of Infection and Chemotherapy : Official Journal of the Japan Society of Chemotherapy·Chih-Cheng LaiPo-Ren Hsueh
Jan 7, 2015·Journal of the American Society for Mass Spectrometry·Sheng-Yu LinSarah Y Chang
Dec 10, 2014·Trends in Parasitology·Matthias A FügiXue Li Guan
Apr 24, 2009·FEMS Yeast Research·Ana Teresa Pinto e SilvaAcácio Gonçalves Rodrigues
Apr 5, 2014·Journal of the American Chemical Society·Zhihai KeYing-Yeung Yeung
Nov 18, 2016·PLoS Neglected Tropical Diseases·Frédéric-Antoine DauchyDerrick R Robinson
Apr 11, 2018·Expert Opinion on Drug Metabolism & Toxicology·Aditya K GuptaNeil H Shear
May 4, 2005·Yeast
Jan 31, 2009·American Journal of Health-system Pharmacy : AJHP : Official Journal of the American Society of Health-System Pharmacists·Michele I Morris
Jul 7, 2020·Chemical Communications : Chem Comm·Esteban MatadorJosé M Lassaletta
Jul 22, 2005·Drugs·Gillian M Keating
Oct 21, 2015·Pharmacy : Journal of Pharmacy, Education and Practice·Simon LeungJade Machin
May 23, 2018·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Christoph MüllerUlrike Binder
Sep 15, 2019·Molecular Diversity·Jyoti Sankar Prusty, Awanish Kumar
Dec 3, 2020·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·Ouli XiaoXiaofeng Dai
Nov 29, 2016·Antiviral Research·Wei SunWei Zheng
Feb 3, 2006·Journal of Medicinal Chemistry·Gustavo BenaimJulio A Urbina

❮ Previous
Next ❯

Related Concepts

Related Feeds

Candidiasis (ASM)

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Aspergillosis (ASM)

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Antifungals

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

CRISPR Screens in Drug Resistance

CRISPR-Cas system enables the editing of genes to create or correct mutations. This feed focuses on the application of CRISPR-Cas system in high-throughput genome-wide screens to identify genes that may confer drug resistance.

Candidiasis

Candidiasis is a common fungal infection caused by Candida and it can affect many parts for the body including mucosal membranes as well as the gastrointestinal, urinary, and respiratory tracts. Here is the latest research.

Aspergillosis

Aspergillosis is the name given to a wide variety of diseases caused by infection by fungi of the genus Aspergillus. Aspergillosis occurs in chronic or acute forms which are clinically very distinct. Most cases of acute aspergillosis occur in patients with severely compromised immune systems. Chronic colonization or infection can cause complications in people with underlying respiratory illnesses. Discover the latest research on aspergillosis here.

Antifungals (ASM)

An antifungal, also known as an antimycotic medication, is a pharmaceutical fungicide or fungistatic used to treat and prevent mycosis such as athlete's foot, ringworm, candidiasis, cryptococcal meningitis, and others. Discover the latest research on antifungals here.

Candida albicans

Candida albicans is an opportunistic, fungal pathogen of humans that frequently causes superficial infections of oral and vaginal mucosal surfaces of debilitated and susceptible individuals. Discover the latest research on Candida albicans here.