3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi
A new experimental protocol: preparation and one step reaction at low temperature (0 °C) in 10 min of reaction (100%). We have synthesized the Morita–Baylis–Hillman adduct (MBHA) 3-hydroxy-2-methylene-3-(4-nitrophenyl)-propanenitrile ( 3) in quantitative yield and evaluated on Trypanosoma cruzi epim...
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| Veröffentlicht in: | Bioorganic chemistry 2010-10, Vol.38 (5), p.190-195 |
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| creator | Sandes, Jana M. Borges, Andrezza R. Junior, Cláudio G.L. Silva, Fábio P.L. Carvalho, Gabriel A.U. Rocha, Gerd B. Vasconcellos, Mário L.A.A. Figueiredo, Regina C.B.Q. |
| description | A new experimental protocol: preparation and one step reaction at low temperature (0
°C) in 10
min of reaction (100%).
We have synthesized the Morita–Baylis–Hillman adduct (MBHA) 3-hydroxy-2-methylene-3-(4-nitrophenyl)-propanenitrile (
3) in quantitative yield and evaluated on
Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms. Compound
3 strongly inhibited epimastigote growth, with IC
50/72
h
of 28.5
μM and also caused intense trypomastigotes lysis, with an IC
50/24
h of 25.5
μM. Ultrastructural analysis showed significant morphological changes on both parasite forms treated with
3, including increase of cell volume and rounding of cell body as well as intense intracellular disorganization. Morphological changes indicative of apoptosis, autophagy or necrosis were observed in most affected cells. Docking calculations of
1,
2 and
3 pointed out the possibility of
T. cruzi Farnesyl Pyrophosphate Synthase (
TcFPPS) enzyme inhibition in
3 mechanism of action. |
| doi_str_mv | 10.1016/j.bioorg.2010.06.003 |
| format | Article |
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°C) in 10
min of reaction (100%).
We have synthesized the Morita–Baylis–Hillman adduct (MBHA) 3-hydroxy-2-methylene-3-(4-nitrophenyl)-propanenitrile (
3) in quantitative yield and evaluated on
Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms. Compound
3 strongly inhibited epimastigote growth, with IC
50/72
h
of 28.5
μM and also caused intense trypomastigotes lysis, with an IC
50/24
h of 25.5
μM. Ultrastructural analysis showed significant morphological changes on both parasite forms treated with
3, including increase of cell volume and rounding of cell body as well as intense intracellular disorganization. Morphological changes indicative of apoptosis, autophagy or necrosis were observed in most affected cells. Docking calculations of
1,
2 and
3 pointed out the possibility of
T. cruzi Farnesyl Pyrophosphate Synthase (
TcFPPS) enzyme inhibition in
3 mechanism of action.</description><identifier>ISSN: 0045-2068</identifier><identifier>EISSN: 1090-2120</identifier><identifier>DOI: 10.1016/j.bioorg.2010.06.003</identifier><identifier>PMID: 20638707</identifier><language>eng</language><publisher>United States: Elsevier Inc</publisher><subject>Acrylonitrile - analogs & derivatives ; Acrylonitrile - chemical synthesis ; Acrylonitrile - pharmacology ; Adducts ; Anti- Trypanosoma cruzi activity ; Benzyl Alcohols - chemical synthesis ; Benzyl Alcohols - pharmacology ; Chagas Disease - drug therapy ; Humans ; Inhibitory Concentration 50 ; Models, Molecular ; Morita–Baylis–Hillman adducts ; Trypanocidal Agents - chemical synthesis ; Trypanocidal Agents - pharmacology ; Trypanosoma cruzi ; Trypanosoma cruzi - drug effects ; Trypanosoma cruzi - growth & development</subject><ispartof>Bioorganic chemistry, 2010-10, Vol.38 (5), p.190-195</ispartof><rights>2010 Elsevier Inc.</rights><rights>2010 Elsevier Inc. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c393t-2ecdd0a4fb567e6cb050448403779de724772353ea312c904195b821a3e721ca3</citedby><cites>FETCH-LOGICAL-c393t-2ecdd0a4fb567e6cb050448403779de724772353ea312c904195b821a3e721ca3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bioorg.2010.06.003$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20638707$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Sandes, Jana M.</creatorcontrib><creatorcontrib>Borges, Andrezza R.</creatorcontrib><creatorcontrib>Junior, Cláudio G.L.</creatorcontrib><creatorcontrib>Silva, Fábio P.L.</creatorcontrib><creatorcontrib>Carvalho, Gabriel A.U.</creatorcontrib><creatorcontrib>Rocha, Gerd B.</creatorcontrib><creatorcontrib>Vasconcellos, Mário L.A.A.</creatorcontrib><creatorcontrib>Figueiredo, Regina C.B.Q.</creatorcontrib><title>3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi</title><title>Bioorganic chemistry</title><addtitle>Bioorg Chem</addtitle><description>A new experimental protocol: preparation and one step reaction at low temperature (0
°C) in 10
min of reaction (100%).
We have synthesized the Morita–Baylis–Hillman adduct (MBHA) 3-hydroxy-2-methylene-3-(4-nitrophenyl)-propanenitrile (
3) in quantitative yield and evaluated on
Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms. Compound
3 strongly inhibited epimastigote growth, with IC
50/72
h
of 28.5
μM and also caused intense trypomastigotes lysis, with an IC
50/24
h of 25.5
μM. Ultrastructural analysis showed significant morphological changes on both parasite forms treated with
3, including increase of cell volume and rounding of cell body as well as intense intracellular disorganization. Morphological changes indicative of apoptosis, autophagy or necrosis were observed in most affected cells. Docking calculations of
1,
2 and
3 pointed out the possibility of
T. cruzi Farnesyl Pyrophosphate Synthase (
TcFPPS) enzyme inhibition in
3 mechanism of action.</description><subject>Acrylonitrile - analogs & derivatives</subject><subject>Acrylonitrile - chemical synthesis</subject><subject>Acrylonitrile - pharmacology</subject><subject>Adducts</subject><subject>Anti- Trypanosoma cruzi activity</subject><subject>Benzyl Alcohols - chemical synthesis</subject><subject>Benzyl Alcohols - pharmacology</subject><subject>Chagas Disease - drug therapy</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Models, Molecular</subject><subject>Morita–Baylis–Hillman adducts</subject><subject>Trypanocidal Agents - chemical synthesis</subject><subject>Trypanocidal Agents - pharmacology</subject><subject>Trypanosoma cruzi</subject><subject>Trypanosoma cruzi - drug effects</subject><subject>Trypanosoma cruzi - growth & development</subject><issn>0045-2068</issn><issn>1090-2120</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNqFkc9u1DAQxiMEokvhDRDyDTh4Gf9JnHBAqqpCkSpxKWfLcSa7XiVxsJ1C-h68L15tgRucPPq-bzya-RXFSwZbBqx6d9i2zvuw23LIElRbAPGo2DBogHLG4XGxAZAl5VDVZ8WzGA8AjElVPS3OsiZqBWpT_BT0eu2C_7FSTkdM-3XACamgbySdXAp-3uO0DnMuzIRHxQ349j25IBN-J3u32w8rMTa5OyTWj7Nfpo6YnXFTTARnN5qY3M4nJCYbKayz_yv1PozE9-Q2y2byMVvEhuXePS-e9GaI-OLhPS--fry6vbymN18-fb68uKFWNCJRjrbrwMi-LSuFlW2hBClrCUKppkPFpVJclAKNYNw2IFlTtjVnRmSPWSPOi9enf_N-3xaMSY8uWhyGvKtfom5YDVI0wP-bVLJuylo2dU7KU9IGH2PAXs8hnyGsmoE-ktMHfSKnj-Q0VDqTy22vHgYs7Yjdn6bfqHLgwymA-SB3DoOO1uFksXMBbdKdd_-e8AvAi63U</recordid><startdate>201010</startdate><enddate>201010</enddate><creator>Sandes, Jana M.</creator><creator>Borges, Andrezza R.</creator><creator>Junior, Cláudio G.L.</creator><creator>Silva, Fábio P.L.</creator><creator>Carvalho, Gabriel A.U.</creator><creator>Rocha, Gerd B.</creator><creator>Vasconcellos, Mário L.A.A.</creator><creator>Figueiredo, Regina C.B.Q.</creator><general>Elsevier Inc</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>7X8</scope><scope>M7N</scope></search><sort><creationdate>201010</creationdate><title>3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi</title><author>Sandes, Jana M. ; Borges, Andrezza R. ; Junior, Cláudio G.L. ; Silva, Fábio P.L. ; Carvalho, Gabriel A.U. ; Rocha, Gerd B. ; Vasconcellos, Mário L.A.A. ; Figueiredo, Regina C.B.Q.</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c393t-2ecdd0a4fb567e6cb050448403779de724772353ea312c904195b821a3e721ca3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>Acrylonitrile - analogs & derivatives</topic><topic>Acrylonitrile - chemical synthesis</topic><topic>Acrylonitrile - pharmacology</topic><topic>Adducts</topic><topic>Anti- Trypanosoma cruzi activity</topic><topic>Benzyl Alcohols - chemical synthesis</topic><topic>Benzyl Alcohols - pharmacology</topic><topic>Chagas Disease - drug therapy</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Models, Molecular</topic><topic>Morita–Baylis–Hillman adducts</topic><topic>Trypanocidal Agents - chemical synthesis</topic><topic>Trypanocidal Agents - pharmacology</topic><topic>Trypanosoma cruzi</topic><topic>Trypanosoma cruzi - drug effects</topic><topic>Trypanosoma cruzi - growth & development</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Sandes, Jana M.</creatorcontrib><creatorcontrib>Borges, Andrezza R.</creatorcontrib><creatorcontrib>Junior, Cláudio G.L.</creatorcontrib><creatorcontrib>Silva, Fábio P.L.</creatorcontrib><creatorcontrib>Carvalho, Gabriel A.U.</creatorcontrib><creatorcontrib>Rocha, Gerd B.</creatorcontrib><creatorcontrib>Vasconcellos, Mário L.A.A.</creatorcontrib><creatorcontrib>Figueiredo, Regina C.B.Q.</creatorcontrib><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><collection>Algology Mycology and Protozoology Abstracts (Microbiology C)</collection><jtitle>Bioorganic chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Sandes, Jana M.</au><au>Borges, Andrezza R.</au><au>Junior, Cláudio G.L.</au><au>Silva, Fábio P.L.</au><au>Carvalho, Gabriel A.U.</au><au>Rocha, Gerd B.</au><au>Vasconcellos, Mário L.A.A.</au><au>Figueiredo, Regina C.B.Q.</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi</atitle><jtitle>Bioorganic chemistry</jtitle><addtitle>Bioorg Chem</addtitle><date>2010-10</date><risdate>2010</risdate><volume>38</volume><issue>5</issue><spage>190</spage><epage>195</epage><pages>190-195</pages><issn>0045-2068</issn><eissn>1090-2120</eissn><abstract>A new experimental protocol: preparation and one step reaction at low temperature (0
°C) in 10
min of reaction (100%).
We have synthesized the Morita–Baylis–Hillman adduct (MBHA) 3-hydroxy-2-methylene-3-(4-nitrophenyl)-propanenitrile (
3) in quantitative yield and evaluated on
Trypanosoma cruzi epimastigote and bloodstream trypomastigote forms. Compound
3 strongly inhibited epimastigote growth, with IC
50/72
h
of 28.5
μM and also caused intense trypomastigotes lysis, with an IC
50/24
h of 25.5
μM. Ultrastructural analysis showed significant morphological changes on both parasite forms treated with
3, including increase of cell volume and rounding of cell body as well as intense intracellular disorganization. Morphological changes indicative of apoptosis, autophagy or necrosis were observed in most affected cells. Docking calculations of
1,
2 and
3 pointed out the possibility of
T. cruzi Farnesyl Pyrophosphate Synthase (
TcFPPS) enzyme inhibition in
3 mechanism of action.</abstract><cop>United States</cop><pub>Elsevier Inc</pub><pmid>20638707</pmid><doi>10.1016/j.bioorg.2010.06.003</doi><tpages>6</tpages></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0045-2068 |
| ispartof | Bioorganic chemistry, 2010-10, Vol.38 (5), p.190-195 |
| issn | 0045-2068 1090-2120 |
| language | eng |
| recordid | cdi_proquest_miscellaneous_918043902 |
| source | MEDLINE; ScienceDirect Journals (5 years ago - present) |
| subjects | Acrylonitrile - analogs & derivatives Acrylonitrile - chemical synthesis Acrylonitrile - pharmacology Adducts Anti- Trypanosoma cruzi activity Benzyl Alcohols - chemical synthesis Benzyl Alcohols - pharmacology Chagas Disease - drug therapy Humans Inhibitory Concentration 50 Models, Molecular Morita–Baylis–Hillman adducts Trypanocidal Agents - chemical synthesis Trypanocidal Agents - pharmacology Trypanosoma cruzi Trypanosoma cruzi - drug effects Trypanosoma cruzi - growth & development |
| title | 3-Hydroxy-2-methylene-3-(4-nitrophenylpropanenitrile): A new highly active compound against epimastigote and trypomastigote form of Trypanosoma cruzi |
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