Synthesis and antifungal activity of new thienyl and aryl conazoles
Recent studies reported that an first generation azole (tioconazole) was active against Candida glabrata petite mutants, a fluconazole- and voriconazole- resistant strain of fungi characterized as most azole resistant yeast by an overexpression of the efflux pumps. Therefore, monosubstituted 1-[2-(2...
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| Veröffentlicht in: | Journal of enzyme inhibition and medicinal chemistry 2006-06, Vol.21 (3), p.293-303 |
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| container_title | Journal of enzyme inhibition and medicinal chemistry |
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| creator | Chevreuil, Francis Landreau, Anne Seraphin, Denis Larcher, GÉrald Bouchara, Jean-Philippe Richomme, Pascal |
| description | Recent studies reported that an first generation azole (tioconazole) was active against Candida glabrata petite mutants, a fluconazole- and voriconazole- resistant strain of fungi characterized as most azole resistant yeast by an overexpression of the efflux pumps. Therefore, monosubstituted 1-[2-(2,4-dichlorophenyl)ethyl]-1H-imidazoles differing from tioconazole by the nature of the linker and of the aromatic ring in their side-chain were synthesized and evaluated against the mutant and the wild-type strain of C. glabrata. New 2-aryl-1-azolyl-3-thienylbutan-2-ols were then designed and synthesized, and their antifungal activity was evaluated against both strains of C. glabrata and two other major human pathogenic fungi, C. albicans and Aspergillus fumigatus. These new compounds exhibited a broad spectrum activity, as well as good efficiency against the petite mutant, suggesting that they may overcome the increased expression of the efflux pumps usually observed in clinical yeast isolates resistant to current azoles. |
| doi_str_mv | 10.1080/14756360600700640 |
| format | Article |
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Therefore, monosubstituted 1-[2-(2,4-dichlorophenyl)ethyl]-1H-imidazoles differing from tioconazole by the nature of the linker and of the aromatic ring in their side-chain were synthesized and evaluated against the mutant and the wild-type strain of C. glabrata. New 2-aryl-1-azolyl-3-thienylbutan-2-ols were then designed and synthesized, and their antifungal activity was evaluated against both strains of C. glabrata and two other major human pathogenic fungi, C. albicans and Aspergillus fumigatus. 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These new compounds exhibited a broad spectrum activity, as well as good efficiency against the petite mutant, suggesting that they may overcome the increased expression of the efflux pumps usually observed in clinical yeast isolates resistant to current azoles.</description><subject>Antifungal agents</subject><subject>Antifungal Agents - chemical synthesis</subject><subject>Antifungal Agents - chemistry</subject><subject>Antifungal Agents - pharmacology</subject><subject>Aspergillus fumigatus</subject><subject>Aspergillus fumigatus - drug effects</subject><subject>azole resistance</subject><subject>Azoles - chemical synthesis</subject><subject>Azoles - chemistry</subject><subject>Azoles - pharmacology</subject><subject>Candida albicans - drug effects</subject><subject>Candida glabrata</subject><subject>Candida glabrata - drug effects</subject><subject>conazole derivatives</subject><subject>Drug Design</subject><subject>efflux pumps</subject><subject>Imidazoles - chemical synthesis</subject><subject>Imidazoles - chemistry</subject><subject>Imidazoles - pharmacology</subject><subject>In Vitro Techniques</subject><subject>Microbial Sensitivity Tests</subject><subject>Molecular Structure</subject><subject>Species Specificity</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><issn>1475-6366</issn><issn>1475-6374</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2006</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkEtLAzEUhYMotlZ_gBuZlbvRm3kkM-hGii8ouFDXIUkzNiVNapKxjL_eKS2KCHVxyb253zkkB6FTDBcYKrjEBS1JToAAUABSwB4aru9SktNi_7snZICOQpgDZDjDxSEaYFLjCigdovFzZ-NMBR0Sbqd9Rd209o2bhMuoP3TsEtckVq2SONPKdmaD-b6RzvJPZ1Q4RgcNN0GdbM8Rer27fRk_pJOn-8fxzSSVZVHENFeipE1FOaZ5XWV5KXAtS1xhUgFUfL2FUta44FJgEIIXeabqqch4Keq6n0bofOO79O69VSGyhQ5SGcOtcm1gpKKkBpr9C2aQAcH52hFvQOldCF41bOn1ov8dw8DWEbM_Efeas615KxZq-qPYZtoD1xtA28b5BV85b6Ys8s4433hupQ4s3-V_9Us-U9zEmeResblrve0T3vG6L8i4mrU</recordid><startdate>20060601</startdate><enddate>20060601</enddate><creator>Chevreuil, Francis</creator><creator>Landreau, Anne</creator><creator>Seraphin, Denis</creator><creator>Larcher, GÉrald</creator><creator>Bouchara, Jean-Philippe</creator><creator>Richomme, Pascal</creator><general>Informa UK Ltd</general><general>Taylor & Francis</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7QO</scope><scope>7T7</scope><scope>8FD</scope><scope>C1K</scope><scope>FR3</scope><scope>M7N</scope><scope>P64</scope><scope>7X8</scope></search><sort><creationdate>20060601</creationdate><title>Synthesis and antifungal activity of new thienyl and aryl conazoles</title><author>Chevreuil, Francis ; 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| subjects | Antifungal agents Antifungal Agents - chemical synthesis Antifungal Agents - chemistry Antifungal Agents - pharmacology Aspergillus fumigatus Aspergillus fumigatus - drug effects azole resistance Azoles - chemical synthesis Azoles - chemistry Azoles - pharmacology Candida albicans - drug effects Candida glabrata Candida glabrata - drug effects conazole derivatives Drug Design efflux pumps Imidazoles - chemical synthesis Imidazoles - chemistry Imidazoles - pharmacology In Vitro Techniques Microbial Sensitivity Tests Molecular Structure Species Specificity Stereoisomerism Structure-Activity Relationship |
| title | Synthesis and antifungal activity of new thienyl and aryl conazoles |
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