Skip to main content
Top
Published in: European Journal of Clinical Microbiology & Infectious Diseases 11/2008

01-11-2008 | Concise Article

Antifungal activity of 25-azalanosterol against Candida species

Authors: J. Wang, J. Wu

Published in: European Journal of Clinical Microbiology & Infectious Diseases | Issue 11/2008

Login to get access

Abstract

The antifungal properties of 25-azalanosterol was investigated. Compared to normal antifungal reagents, fluoconazole, clotrimazole and voriconazole, it exhibited significant anti-Candida activity (the minimum inhibitory concentration [MIC] ranges were 0.125–8, 0.5–8 and 0.5–32 µg/mL against C. albicans, C. krusei and C. glabrata, respectively), but showed little toxicity to mice liver cells at clinical dosage after 24 h of exposure, with the lowest lactate dehydrogenase and the highest ED50 compared to four other azoles antifungal agents. 25-Azalanosterol inhibited the incorporation of [methyl-3H3] AdoMet into the C-24 of ergosterol in whole cells of C. albicans. Thus, 25-azalanosterol, as an inhibitor of the growth of C. albicans in vitro, may have considerable potential as a new class of anti-Candida agent that lacks toxic side effects in the mammalian host.
Literature
1.
go back to reference Long SS, Stevenson DK (2005) Reducing Candida infections during neonatal intensive care: management choices, infection control, and fluconazole prophylaxis. J Pediatr 147:135–141PubMedCrossRef Long SS, Stevenson DK (2005) Reducing Candida infections during neonatal intensive care: management choices, infection control, and fluconazole prophylaxis. J Pediatr 147:135–141PubMedCrossRef
2.
go back to reference Blyth CC, Palasanthiran P, O’Brien TA (2007) Antifungal therapy in children with invasive fungal infections: a systematic review. Pediatrics 119:772–784PubMedCrossRef Blyth CC, Palasanthiran P, O’Brien TA (2007) Antifungal therapy in children with invasive fungal infections: a systematic review. Pediatrics 119:772–784PubMedCrossRef
3.
go back to reference Pfaller MA, Pappas PG, Wingard JR (2006) Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis 43:S3–S14CrossRef Pfaller MA, Pappas PG, Wingard JR (2006) Invasive fungal pathogens: current epidemiological trends. Clin Infect Dis 43:S3–S14CrossRef
4.
go back to reference Fidel PL Jr, Vazquez JA, Sobel JD (1999) Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Rev 12:80–96PubMed Fidel PL Jr, Vazquez JA, Sobel JD (1999) Candida glabrata: review of epidemiology, pathogenesis, and clinical disease with comparison to C. albicans. Clin Microbiol Rev 12:80–96PubMed
5.
go back to reference Hoppe JE (1997) Treatment of oropharyngeal candidiasis and candidal diaper dermatitis in neonates and infants: review and reappraisal. Pediatr Infect Dis J 16:885–894PubMedCrossRef Hoppe JE (1997) Treatment of oropharyngeal candidiasis and candidal diaper dermatitis in neonates and infants: review and reappraisal. Pediatr Infect Dis J 16:885–894PubMedCrossRef
6.
go back to reference Kauffman CA (2006) Endemic mycoses: blastomycosis, histoplasmosis, and sporotrichosis. Clin Infect Dis N Am 20:645–662CrossRef Kauffman CA (2006) Endemic mycoses: blastomycosis, histoplasmosis, and sporotrichosis. Clin Infect Dis N Am 20:645–662CrossRef
7.
go back to reference Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Grossman LB (2005) Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight. J Pediatr 147:172–179PubMedCrossRef Kaufman D, Boyle R, Hazen KC, Patrie JT, Robinson M, Grossman LB (2005) Twice weekly fluconazole prophylaxis for prevention of invasive Candida infection in high-risk infants of <1000 grams birth weight. J Pediatr 147:172–179PubMedCrossRef
8.
go back to reference Kim CK, Jeon KI, Lim DM, Johng T, Trzaskos JM, Gaylor JL, Paik YK (1995) Cholesterol biosynthesis from lanosterol: regulation and purification of rat hepatic sterol 14-reductase. Biochim Biophys Acta 1259:39–48PubMed Kim CK, Jeon KI, Lim DM, Johng T, Trzaskos JM, Gaylor JL, Paik YK (1995) Cholesterol biosynthesis from lanosterol: regulation and purification of rat hepatic sterol 14-reductase. Biochim Biophys Acta 1259:39–48PubMed
9.
go back to reference Kanagasabai R, Zhou WX, Liu JL, Nguyen TT, Veeramachaneni P, Nes WD (2004) Disruption of ergosterol biosynthesis, growth, and the morphological transition in Candida albicans by sterol methyltransferase inhibitors containing sulfur at C-25 in the sterol side chain. Lipids 39:737–746PubMed Kanagasabai R, Zhou WX, Liu JL, Nguyen TT, Veeramachaneni P, Nes WD (2004) Disruption of ergosterol biosynthesis, growth, and the morphological transition in Candida albicans by sterol methyltransferase inhibitors containing sulfur at C-25 in the sterol side chain. Lipids 39:737–746PubMed
10.
go back to reference Zhou WX, Lepesheva GI, Waterman MR, Nes WD (2006) Mechanistic analysis of a multiple product sterol methyltransferase implicated in ergosterol biosynthesis in Trypanosoma brucei. J Biol Chem 281:6290–6296PubMedCrossRef Zhou WX, Lepesheva GI, Waterman MR, Nes WD (2006) Mechanistic analysis of a multiple product sterol methyltransferase implicated in ergosterol biosynthesis in Trypanosoma brucei. J Biol Chem 281:6290–6296PubMedCrossRef
11.
go back to reference Kaneshiro ES, Rosenfeld JA, Basselin M, Stringer JR, Keely S, Smulian AG, Giner JL (2002) The Pneumocystis carinii drug target S-adenosyl-L-methionine: sterol C-24 methyl transferase has a unique substrate preference. Mol Microbiol 44:989–999PubMedCrossRef Kaneshiro ES, Rosenfeld JA, Basselin M, Stringer JR, Keely S, Smulian AG, Giner JL (2002) The Pneumocystis carinii drug target S-adenosyl-L-methionine: sterol C-24 methyl transferase has a unique substrate preference. Mol Microbiol 44:989–999PubMedCrossRef
12.
go back to reference Zhou WX, Cross GA, Nes WD (2007) Cholesterol import fails to prevent catalyst-based inhibition of ergosterol synthesis and cell proliferation of Trypanosoma brucei. J Lipid Res 48:665–673 Zhou WX, Cross GA, Nes WD (2007) Cholesterol import fails to prevent catalyst-based inhibition of ergosterol synthesis and cell proliferation of Trypanosoma brucei. J Lipid Res 48:665–673
13.
go back to reference Wang JQ, Liu JL, Song ZH, Nes WD (2008) Sterol C24-methyltransferase: mechanistic studies of the C-methylation reaction with 24-fluorocycloartenol. Bioorg Med Chem Lett 18:232–235PubMedCrossRef Wang JQ, Liu JL, Song ZH, Nes WD (2008) Sterol C24-methyltransferase: mechanistic studies of the C-methylation reaction with 24-fluorocycloartenol. Bioorg Med Chem Lett 18:232–235PubMedCrossRef
14.
go back to reference Nes WD, Jayasimha P, Zhou WX, Kanagasabai R, Jin C, Jaradat TT, Shaw RW, Bujnicki JM (2004) Sterol methyltransferase: functional analysis of highly conserved residues by site-directed mutagenesis. Biochemistry 43:569–576PubMedCrossRef Nes WD, Jayasimha P, Zhou WX, Kanagasabai R, Jin C, Jaradat TT, Shaw RW, Bujnicki JM (2004) Sterol methyltransferase: functional analysis of highly conserved residues by site-directed mutagenesis. Biochemistry 43:569–576PubMedCrossRef
15.
go back to reference Arora A, Raghuraman H, Chattopadhyay A (2004) Influence of cholesterol and ergosterol on membrane dynamics: a fluorescence approach. Biochem Biophys Res Commun 318:920–926PubMedCrossRef Arora A, Raghuraman H, Chattopadhyay A (2004) Influence of cholesterol and ergosterol on membrane dynamics: a fluorescence approach. Biochem Biophys Res Commun 318:920–926PubMedCrossRef
16.
go back to reference Deyes R (2002) Cell viability assays. Promega Notes 81:32–33 Deyes R (2002) Cell viability assays. Promega Notes 81:32–33
17.
go back to reference Nanotechnology Characterization Laboratory (NCL) (2006) HEP G2 hepatocarcinoma cytotoxicity assay. NCL Method GTA-2. SAIC-Frederick Inc. pp 3–7 Nanotechnology Characterization Laboratory (NCL) (2006) HEP G2 hepatocarcinoma cytotoxicity assay. NCL Method GTA-2. SAIC-Frederick Inc. pp 3–7
18.
go back to reference Wang JQ, Nes WD (2008) Mechanism and scope of cyclobranol modulated 24-sterol methyltransferase catalysis enzyme inactivation and concurrent C24-alkylation and dealkylation. J Biol Chem (in Press) Wang JQ, Nes WD (2008) Mechanism and scope of cyclobranol modulated 24-sterol methyltransferase catalysis enzyme inactivation and concurrent C24-alkylation and dealkylation. J Biol Chem (in Press)
19.
go back to reference Worsham DN, Basselin M, Smulian AG, Beach DH, Kaneshiro ES (2003) Evidence for cholesterol scavenging by Pneumocystis and potential modifications of host-synthesized sterols by the P. carinii SAM:SMT. J Eukaryot Microbiol 50:678–679PubMedCrossRef Worsham DN, Basselin M, Smulian AG, Beach DH, Kaneshiro ES (2003) Evidence for cholesterol scavenging by Pneumocystis and potential modifications of host-synthesized sterols by the P. carinii SAM:SMT. J Eukaryot Microbiol 50:678–679PubMedCrossRef
20.
go back to reference Smith PB, Steinbach WJ, Benjamin DK Jr (2005) Neonatal candidiasis. Infect Dis Clin North Am 19:603–615PubMedCrossRef Smith PB, Steinbach WJ, Benjamin DK Jr (2005) Neonatal candidiasis. Infect Dis Clin North Am 19:603–615PubMedCrossRef
21.
go back to reference Zaoutis TE, Heydon K, Localio R, Walsh TJ, Feudtner C (2007) Outcomes attributable to neonatal candidiasis. Clin Infect Dis 44:1187–1193PubMedCrossRef Zaoutis TE, Heydon K, Localio R, Walsh TJ, Feudtner C (2007) Outcomes attributable to neonatal candidiasis. Clin Infect Dis 44:1187–1193PubMedCrossRef
22.
go back to reference Song ZH, Zhou WX, Liu JL, Nes WD (2004) Mechanism-based active site modification of the soybean sterol methyltransferase by 26,27-dehydrocycloartenol. Bioorg Med Chem Lett 14:33–36PubMedCrossRef Song ZH, Zhou WX, Liu JL, Nes WD (2004) Mechanism-based active site modification of the soybean sterol methyltransferase by 26,27-dehydrocycloartenol. Bioorg Med Chem Lett 14:33–36PubMedCrossRef
23.
go back to reference Taylor FR, Rodriguez RJ, Parks LW (1983) Relationship between antifungal activity and inhibition of sterol biosynthesis in miconazole, clotrimazole, and 15-azasterol. Antimicrob Agents Chemother 23:515–521PubMed Taylor FR, Rodriguez RJ, Parks LW (1983) Relationship between antifungal activity and inhibition of sterol biosynthesis in miconazole, clotrimazole, and 15-azasterol. Antimicrob Agents Chemother 23:515–521PubMed
24.
go back to reference Borgers M, Van den Bossche H (1982) The mode of action of antifungal drugs. Ketoconazole in the management of fungal disease. Adis Press, New York, pp 25–47 Borgers M, Van den Bossche H (1982) The mode of action of antifungal drugs. Ketoconazole in the management of fungal disease. Adis Press, New York, pp 25–47
Metadata
Title
Antifungal activity of 25-azalanosterol against Candida species
Authors
J. Wang
J. Wu
Publication date
01-11-2008
Publisher
Springer-Verlag
Published in
European Journal of Clinical Microbiology & Infectious Diseases / Issue 11/2008
Print ISSN: 0934-9723
Electronic ISSN: 1435-4373
DOI
https://doi.org/10.1007/s10096-008-0554-y

Other articles of this Issue 11/2008

European Journal of Clinical Microbiology & Infectious Diseases 11/2008 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.