Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines
The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemi...
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| Veröffentlicht in: | European journal of medicinal chemistry 2008-12, Vol.43 (12), p.2665-2676 |
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| container_title | European journal of medicinal chemistry |
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| creator | SCHENONE, Silvia BRULLO, Chiara BOTTA, Maurizio BRUNO, Olga BONDAVALLI, Francesco MOSTI, Luisa MAGA, Giovanni CRESPAN, Emmanuele CARRARO, Fabio MANETTI, Fabrizio TINTORI, Cristina |
| description | The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl. |
| doi_str_mv | 10.1016/j.ejmech.2008.01.034 |
| format | Article |
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Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2008.01.034</identifier><identifier>PMID: 18342402</identifier><identifier>CODEN: EJMCA5</identifier><language>eng</language><publisher>Kidlington: Elsevier</publisher><subject>Antineoplastic agents ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Cell Proliferation - drug effects ; Computer Simulation ; Drug Screening Assays, Antitumor ; Fusion Proteins, bcr-abl - antagonists & inhibitors ; General aspects ; Humans ; Medical sciences ; Models, Chemical ; Molecular Structure ; Pharmacology. Drug treatments ; Protein Kinase Inhibitors - chemical synthesis ; Protein Kinase Inhibitors - chemistry ; Protein Kinase Inhibitors - pharmacology ; Protein-Tyrosine Kinases - antagonists & inhibitors ; Pyrazoles - chemistry ; Pyrimidines - chemical synthesis ; Pyrimidines - chemistry ; Pyrimidines - pharmacology ; Recombinant Proteins - antagonists & inhibitors ; src-Family Kinases ; Stereoisomerism ; Structure-Activity Relationship ; Tumor Cells, Cultured</subject><ispartof>European journal of medicinal chemistry, 2008-12, Vol.43 (12), p.2665-2676</ispartof><rights>2009 INIST-CNRS</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c401t-6504b50788569c1049f2456aa99618b25331efa7e371104c30830d6ef68d7a893</citedby><cites>FETCH-LOGICAL-c401t-6504b50788569c1049f2456aa99618b25331efa7e371104c30830d6ef68d7a893</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>314,776,780,27903,27904</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=20985711$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/18342402$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>SCHENONE, Silvia</creatorcontrib><creatorcontrib>BRULLO, Chiara</creatorcontrib><creatorcontrib>BOTTA, Maurizio</creatorcontrib><creatorcontrib>BRUNO, Olga</creatorcontrib><creatorcontrib>BONDAVALLI, Francesco</creatorcontrib><creatorcontrib>MOSTI, Luisa</creatorcontrib><creatorcontrib>MAGA, Giovanni</creatorcontrib><creatorcontrib>CRESPAN, Emmanuele</creatorcontrib><creatorcontrib>CARRARO, Fabio</creatorcontrib><creatorcontrib>MANETTI, Fabrizio</creatorcontrib><creatorcontrib>TINTORI, Cristina</creatorcontrib><title>Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl.</description><subject>Antineoplastic agents</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Biological and medical sciences</subject><subject>Cell Proliferation - drug effects</subject><subject>Computer Simulation</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Fusion Proteins, bcr-abl - antagonists & inhibitors</subject><subject>General aspects</subject><subject>Humans</subject><subject>Medical sciences</subject><subject>Models, Chemical</subject><subject>Molecular Structure</subject><subject>Pharmacology. Drug treatments</subject><subject>Protein Kinase Inhibitors - chemical synthesis</subject><subject>Protein Kinase Inhibitors - chemistry</subject><subject>Protein Kinase Inhibitors - pharmacology</subject><subject>Protein-Tyrosine Kinases - antagonists & inhibitors</subject><subject>Pyrazoles - chemistry</subject><subject>Pyrimidines - chemical synthesis</subject><subject>Pyrimidines - chemistry</subject><subject>Pyrimidines - pharmacology</subject><subject>Recombinant Proteins - antagonists & inhibitors</subject><subject>src-Family Kinases</subject><subject>Stereoisomerism</subject><subject>Structure-Activity Relationship</subject><subject>Tumor Cells, Cultured</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2008</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpFkE1r3DAQhkVoaLZp_0EourSn2B19Wj6G0DaBQA9tT6UIWZITbW1r47ED219fhV3S0zDM874MDyEXDGoGTH_a1nE7Rv9QcwBTA6tByBOyYY02leBKviIb4FxUigt5Rt4gbgFAaYDX5IwZIbkEviHp-35aHiImvKRdykO-T94NND65YXVLyhN1U6Ah-z9puqe4rCFFpLmnsnJjmjLFtcMlLesSA2U31W4_u7-l5pe4lFX4XdY0ppCmiG_Jae8GjO-O85z8_PL5x_VNdfft6-311V3lJbCl0gpkp6AxRunWM5Btz6XSzrWtZqbjSggWe9dE0bBy9QKMgKBjr01onGnFOfl46N3N-XGNuNgxoY_D4KaYV7S6NZpLbQooD6CfM-Ice7srz7p5bxnYZ8V2aw-K7bNiC8wWxSX2_ti_dmMM_0NHpwX4cAQcFpf97Caf8IXj0BpVfhf_AMpMhes</recordid><startdate>20081201</startdate><enddate>20081201</enddate><creator>SCHENONE, Silvia</creator><creator>BRULLO, Chiara</creator><creator>BOTTA, Maurizio</creator><creator>BRUNO, Olga</creator><creator>BONDAVALLI, Francesco</creator><creator>MOSTI, Luisa</creator><creator>MAGA, Giovanni</creator><creator>CRESPAN, Emmanuele</creator><creator>CARRARO, Fabio</creator><creator>MANETTI, Fabrizio</creator><creator>TINTORI, Cristina</creator><general>Elsevier</general><scope>IQODW</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>20081201</creationdate><title>Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines</title><author>SCHENONE, Silvia ; BRULLO, Chiara ; BOTTA, Maurizio ; BRUNO, Olga ; BONDAVALLI, Francesco ; MOSTI, Luisa ; MAGA, Giovanni ; CRESPAN, Emmanuele ; CARRARO, Fabio ; MANETTI, Fabrizio ; TINTORI, Cristina</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c401t-6504b50788569c1049f2456aa99618b25331efa7e371104c30830d6ef68d7a893</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2008</creationdate><topic>Antineoplastic agents</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Biological and medical sciences</topic><topic>Cell Proliferation - drug effects</topic><topic>Computer Simulation</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Fusion Proteins, bcr-abl - antagonists & inhibitors</topic><topic>General aspects</topic><topic>Humans</topic><topic>Medical sciences</topic><topic>Models, Chemical</topic><topic>Molecular Structure</topic><topic>Pharmacology. Drug treatments</topic><topic>Protein Kinase Inhibitors - chemical synthesis</topic><topic>Protein Kinase Inhibitors - chemistry</topic><topic>Protein Kinase Inhibitors - pharmacology</topic><topic>Protein-Tyrosine Kinases - antagonists & inhibitors</topic><topic>Pyrazoles - chemistry</topic><topic>Pyrimidines - chemical synthesis</topic><topic>Pyrimidines - chemistry</topic><topic>Pyrimidines - pharmacology</topic><topic>Recombinant Proteins - antagonists & inhibitors</topic><topic>src-Family Kinases</topic><topic>Stereoisomerism</topic><topic>Structure-Activity Relationship</topic><topic>Tumor Cells, Cultured</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>SCHENONE, Silvia</creatorcontrib><creatorcontrib>BRULLO, Chiara</creatorcontrib><creatorcontrib>BOTTA, Maurizio</creatorcontrib><creatorcontrib>BRUNO, Olga</creatorcontrib><creatorcontrib>BONDAVALLI, Francesco</creatorcontrib><creatorcontrib>MOSTI, Luisa</creatorcontrib><creatorcontrib>MAGA, Giovanni</creatorcontrib><creatorcontrib>CRESPAN, Emmanuele</creatorcontrib><creatorcontrib>CARRARO, Fabio</creatorcontrib><creatorcontrib>MANETTI, Fabrizio</creatorcontrib><creatorcontrib>TINTORI, Cristina</creatorcontrib><collection>Pascal-Francis</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>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>SCHENONE, Silvia</au><au>BRULLO, Chiara</au><au>BOTTA, Maurizio</au><au>BRUNO, Olga</au><au>BONDAVALLI, Francesco</au><au>MOSTI, Luisa</au><au>MAGA, Giovanni</au><au>CRESPAN, Emmanuele</au><au>CARRARO, Fabio</au><au>MANETTI, Fabrizio</au><au>TINTORI, Cristina</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2008-12-01</date><risdate>2008</risdate><volume>43</volume><issue>12</issue><spage>2665</spage><epage>2676</epage><pages>2665-2676</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><coden>EJMCA5</coden><abstract>The synthesis of new 4-amino substituted pyrazolo[3,4-d]pyrimidines along with their activity in cell-free enzymatic assays on Src and Abl tyrosine kinases is reported. Some compounds emerged as good dual inhibitors of the two enzymes, showed antiproliferative effects on two Bcr-Abl positive leukemia cell lines K-562 and KU-812, and induced apoptosis, as demonstrated by the PARP assay. Docking studies have been also performed to analyze the binding mode of compounds under study and to identify the structural determinants of their interaction with both Src and Abl.</abstract><cop>Kidlington</cop><pub>Elsevier</pub><pmid>18342402</pmid><doi>10.1016/j.ejmech.2008.01.034</doi><tpages>12</tpages></addata></record> |
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| subjects | Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biological and medical sciences Cell Proliferation - drug effects Computer Simulation Drug Screening Assays, Antitumor Fusion Proteins, bcr-abl - antagonists & inhibitors General aspects Humans Medical sciences Models, Chemical Molecular Structure Pharmacology. Drug treatments Protein Kinase Inhibitors - chemical synthesis Protein Kinase Inhibitors - chemistry Protein Kinase Inhibitors - pharmacology Protein-Tyrosine Kinases - antagonists & inhibitors Pyrazoles - chemistry Pyrimidines - chemical synthesis Pyrimidines - chemistry Pyrimidines - pharmacology Recombinant Proteins - antagonists & inhibitors src-Family Kinases Stereoisomerism Structure-Activity Relationship Tumor Cells, Cultured |
| title | Synthesis, biological evaluation and docking studies of 4-amino substituted 1H-pyrazolo[3,4-d]pyrimidines |
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