Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents
New Mannich base‐type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate (7) and 4‐{5‐allyl‐2‐[(4‐chlorobenzoyl)oxy]‐3‐methoxybenzyl}morpholi...
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| Veröffentlicht in: | Chemical biology & drug design 2015-10, Vol.86 (4), p.459-465 |
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| creator | Abrão, Pedro Henrique O. Pizi, Rafael B. de Souza, Thiago B. Silva, Naiara C. Fregnan, Antonio M. Silva, Fernanda N. Coelho, Luiz Felipe L. Malaquias, Luiz Cosme C. Dias, Amanda Latercia T. Dias, Danielle F. Veloso, Marcia P. Carvalho, Diogo T. |
| description | New Mannich base‐type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate (7) and 4‐{5‐allyl‐2‐[(4‐chlorobenzoyl)oxy]‐3‐methoxybenzyl}morpholin‐4‐ium chloride (8) were found to be the most effective antifungal compounds with low IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C. glabrata (1.23 μm), C. albicans and C. krusei (both 0.63 μm). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and they also presented high selectivity indexes.
A series of new eugenol derivatives was synthesized and evaluated for its anticandidal activities. The morpholinyl Mannich base 7 (4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate) showed high antifungal activity (IC50 0.63 μm) and an expressive selectivity index (600.0) against Candida albicans and Candida krusei. |
| doi_str_mv | 10.1111/cbdd.12504 |
| format | Article |
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A series of new eugenol derivatives was synthesized and evaluated for its anticandidal activities. The morpholinyl Mannich base 7 (4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate) showed high antifungal activity (IC50 0.63 μm) and an expressive selectivity index (600.0) against Candida albicans and Candida krusei.</description><identifier>ISSN: 1747-0277</identifier><identifier>EISSN: 1747-0285</identifier><identifier>DOI: 10.1111/cbdd.12504</identifier><identifier>PMID: 25556966</identifier><language>eng</language><publisher>England: Blackwell Publishing Ltd</publisher><subject>antifungal action ; Antifungal Agents - chemical synthesis ; Antifungal Agents - chemistry ; Antifungal Agents - pharmacology ; antimicrobial agents ; Candida - growth & development ; Candida sp ; Candidiasis - drug therapy ; Cytotoxins - chemical synthesis ; Cytotoxins - chemistry ; Cytotoxins - pharmacology ; eugenol ; Eugenol - chemistry ; Eugenol - pharmacology ; Humans ; Leukocytes, Mononuclear - cytology ; Leukocytes, Mononuclear - metabolism ; mannich bases</subject><ispartof>Chemical biology & drug design, 2015-10, Vol.86 (4), p.459-465</ispartof><rights>2014 John Wiley & Sons A/S</rights><rights>2014 John Wiley & Sons A/S.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c3674-7a677ad3f09a524565497f659d54fe47eb1c0b106ba72d3c84f749b824e0cdfa3</citedby><cites>FETCH-LOGICAL-c3674-7a677ad3f09a524565497f659d54fe47eb1c0b106ba72d3c84f749b824e0cdfa3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://onlinelibrary.wiley.com/doi/pdf/10.1111%2Fcbdd.12504$$EPDF$$P50$$Gwiley$$H</linktopdf><linktohtml>$$Uhttps://onlinelibrary.wiley.com/doi/full/10.1111%2Fcbdd.12504$$EHTML$$P50$$Gwiley$$H</linktohtml><link.rule.ids>314,780,784,1417,27924,27925,45574,45575</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25556966$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Abrão, Pedro Henrique O.</creatorcontrib><creatorcontrib>Pizi, Rafael B.</creatorcontrib><creatorcontrib>de Souza, Thiago B.</creatorcontrib><creatorcontrib>Silva, Naiara C.</creatorcontrib><creatorcontrib>Fregnan, Antonio M.</creatorcontrib><creatorcontrib>Silva, Fernanda N.</creatorcontrib><creatorcontrib>Coelho, Luiz Felipe L.</creatorcontrib><creatorcontrib>Malaquias, Luiz Cosme C.</creatorcontrib><creatorcontrib>Dias, Amanda Latercia T.</creatorcontrib><creatorcontrib>Dias, Danielle F.</creatorcontrib><creatorcontrib>Veloso, Marcia P.</creatorcontrib><creatorcontrib>Carvalho, Diogo T.</creatorcontrib><title>Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents</title><title>Chemical biology & drug design</title><addtitle>Chem Biol Drug Des</addtitle><description>New Mannich base‐type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate (7) and 4‐{5‐allyl‐2‐[(4‐chlorobenzoyl)oxy]‐3‐methoxybenzyl}morpholin‐4‐ium chloride (8) were found to be the most effective antifungal compounds with low IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C. glabrata (1.23 μm), C. albicans and C. krusei (both 0.63 μm). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and they also presented high selectivity indexes.
A series of new eugenol derivatives was synthesized and evaluated for its anticandidal activities. The morpholinyl Mannich base 7 (4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate) showed high antifungal activity (IC50 0.63 μm) and an expressive selectivity index (600.0) against Candida albicans and Candida krusei.</description><subject>antifungal action</subject><subject>Antifungal Agents - chemical synthesis</subject><subject>Antifungal Agents - chemistry</subject><subject>Antifungal Agents - pharmacology</subject><subject>antimicrobial agents</subject><subject>Candida - growth & development</subject><subject>Candida sp</subject><subject>Candidiasis - drug therapy</subject><subject>Cytotoxins - chemical synthesis</subject><subject>Cytotoxins - chemistry</subject><subject>Cytotoxins - pharmacology</subject><subject>eugenol</subject><subject>Eugenol - chemistry</subject><subject>Eugenol - pharmacology</subject><subject>Humans</subject><subject>Leukocytes, Mononuclear - cytology</subject><subject>Leukocytes, Mononuclear - metabolism</subject><subject>mannich bases</subject><issn>1747-0277</issn><issn>1747-0285</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2015</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtOwzAQRS0E4r3hA5CXCClgJ7YnWbalPMRTPMTSchy7GFIb4gTo3xModMlsZhbnXo0OQjuUHNB-DnVZVQc05YQtoXUKDBKS5nx5cQOsoY0YnwlhjKf5KlpLOeeiEGIdybuZb59MdBErX-GhC3WYOK1qPH5XdadaFzwOFl-ZDzzuJsaHGl8q751-wkMVTR-L-KYJUxedn-CBb53t_KTPD3q4jVtoxao6mu3fvYkejsf3o9Pk4vrkbDS4SHQmgCWgBICqMksKxVPGBWcFWMGLijNrGJiSalJSIkoFaZXpnFlgRZmnzBBdWZVtor1572sT3joTW9l_pE1dK29CFyUFmhMARkWP7s9R3YQYG2Pla-OmqplJSuS3UPktVP4I7eHd396unJpqgf4Z7AE6Bz5cbWb_VMnR8OjorzSZZ1xszecio5oXKSADLh-vTuTtY3F_muXH8jz7AvFgjzs</recordid><startdate>201510</startdate><enddate>201510</enddate><creator>Abrão, Pedro Henrique O.</creator><creator>Pizi, Rafael B.</creator><creator>de Souza, Thiago B.</creator><creator>Silva, Naiara C.</creator><creator>Fregnan, Antonio M.</creator><creator>Silva, Fernanda N.</creator><creator>Coelho, Luiz Felipe L.</creator><creator>Malaquias, Luiz Cosme C.</creator><creator>Dias, Amanda Latercia T.</creator><creator>Dias, Danielle F.</creator><creator>Veloso, Marcia P.</creator><creator>Carvalho, Diogo T.</creator><general>Blackwell Publishing Ltd</general><scope>BSCLL</scope><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>7X8</scope></search><sort><creationdate>201510</creationdate><title>Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents</title><author>Abrão, Pedro Henrique O. ; Pizi, Rafael B. ; de Souza, Thiago B. ; Silva, Naiara C. ; Fregnan, Antonio M. ; Silva, Fernanda N. ; Coelho, Luiz Felipe L. ; Malaquias, Luiz Cosme C. ; Dias, Amanda Latercia T. ; Dias, Danielle F. ; Veloso, Marcia P. ; Carvalho, Diogo T.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c3674-7a677ad3f09a524565497f659d54fe47eb1c0b106ba72d3c84f749b824e0cdfa3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2015</creationdate><topic>antifungal action</topic><topic>Antifungal Agents - chemical synthesis</topic><topic>Antifungal Agents - chemistry</topic><topic>Antifungal Agents - pharmacology</topic><topic>antimicrobial agents</topic><topic>Candida - growth & development</topic><topic>Candida sp</topic><topic>Candidiasis - drug therapy</topic><topic>Cytotoxins - chemical synthesis</topic><topic>Cytotoxins - chemistry</topic><topic>Cytotoxins - pharmacology</topic><topic>eugenol</topic><topic>Eugenol - chemistry</topic><topic>Eugenol - pharmacology</topic><topic>Humans</topic><topic>Leukocytes, Mononuclear - cytology</topic><topic>Leukocytes, Mononuclear - metabolism</topic><topic>mannich bases</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Abrão, Pedro Henrique O.</creatorcontrib><creatorcontrib>Pizi, Rafael B.</creatorcontrib><creatorcontrib>de Souza, Thiago B.</creatorcontrib><creatorcontrib>Silva, Naiara C.</creatorcontrib><creatorcontrib>Fregnan, Antonio M.</creatorcontrib><creatorcontrib>Silva, Fernanda N.</creatorcontrib><creatorcontrib>Coelho, Luiz Felipe L.</creatorcontrib><creatorcontrib>Malaquias, Luiz Cosme C.</creatorcontrib><creatorcontrib>Dias, Amanda Latercia T.</creatorcontrib><creatorcontrib>Dias, Danielle F.</creatorcontrib><creatorcontrib>Veloso, Marcia P.</creatorcontrib><creatorcontrib>Carvalho, Diogo T.</creatorcontrib><collection>Istex</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><jtitle>Chemical biology & drug design</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Abrão, Pedro Henrique O.</au><au>Pizi, Rafael B.</au><au>de Souza, Thiago B.</au><au>Silva, Naiara C.</au><au>Fregnan, Antonio M.</au><au>Silva, Fernanda N.</au><au>Coelho, Luiz Felipe L.</au><au>Malaquias, Luiz Cosme C.</au><au>Dias, Amanda Latercia T.</au><au>Dias, Danielle F.</au><au>Veloso, Marcia P.</au><au>Carvalho, Diogo T.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents</atitle><jtitle>Chemical biology & drug design</jtitle><addtitle>Chem Biol Drug Des</addtitle><date>2015-10</date><risdate>2015</risdate><volume>86</volume><issue>4</issue><spage>459</spage><epage>465</epage><pages>459-465</pages><issn>1747-0277</issn><eissn>1747-0285</eissn><abstract>New Mannich base‐type eugenol derivatives were synthesized and evaluated for their anticandidal activity using a broth microdilution assay. Among the synthesized compounds, 4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate (7) and 4‐{5‐allyl‐2‐[(4‐chlorobenzoyl)oxy]‐3‐methoxybenzyl}morpholin‐4‐ium chloride (8) were found to be the most effective antifungal compounds with low IC50 values, some of them well below those of reference drug fluconazole. The most significant IC50 values were those of 7 against C. glabrata (1.23 μm), C. albicans and C. krusei (both 0.63 μm). Additionally, the synthesized compounds were evaluated for their in vitro cytotoxic effects on human mononuclear cells. As result, the cytotoxic activity of eugenol in eukaryotic cells decreased with the introduction of the morpholinyl group. Given these findings, we point out compounds 7 and 8 as the most promising derivatives because they showed potency values greater than those of eugenol and fluconazole and they also presented high selectivity indexes.
A series of new eugenol derivatives was synthesized and evaluated for its anticandidal activities. The morpholinyl Mannich base 7 (4‐allyl‐2‐methoxy‐6‐(morpholin‐4‐ylmethyl) phenyl benzoate) showed high antifungal activity (IC50 0.63 μm) and an expressive selectivity index (600.0) against Candida albicans and Candida krusei.</abstract><cop>England</cop><pub>Blackwell Publishing Ltd</pub><pmid>25556966</pmid><doi>10.1111/cbdd.12504</doi><tpages>7</tpages></addata></record> |
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| subjects | antifungal action Antifungal Agents - chemical synthesis Antifungal Agents - chemistry Antifungal Agents - pharmacology antimicrobial agents Candida - growth & development Candida sp Candidiasis - drug therapy Cytotoxins - chemical synthesis Cytotoxins - chemistry Cytotoxins - pharmacology eugenol Eugenol - chemistry Eugenol - pharmacology Humans Leukocytes, Mononuclear - cytology Leukocytes, Mononuclear - metabolism mannich bases |
| title | Synthesis and Biological Evaluation of New Eugenol Mannich Bases as Promising Antifungal Agents |
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