A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis
Based on DOCK scores 18 N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters ( 6a– r) were synthesized as anti-tumor agents. Their IC 50 values against five human carcinoma cell lines ranged from 11.1 μM to more than 100 μM. The in vivo assay identified five derivatives of them had no a...
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| Veröffentlicht in: | Bioorganic & medicinal chemistry 2010-09, Vol.18 (17), p.6220-6229 |
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| container_title | Bioorganic & medicinal chemistry |
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| creator | Wu, Jianhui Li, Chunyu Zhao, Ming Wang, Wenjing Wang, Yuji Peng, Shiqi |
| description | Based on DOCK scores 18
N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (
6a–
r) were synthesized as anti-tumor agents. Their IC
50 values against five human carcinoma cell lines ranged from 11.1
μM to more than 100
μM. The in vivo assay identified five derivatives of them had no anti-tumor action, the anti-tumor activity of nine derivatives of them equaled that of cytarabine, and the anti-tumor activity of three derivatives of them was higher than that of cytarabine. The UV and fluorescence spectra, as well as the relative viscosity and melting temperature measurements of calf thymus DNA (CT DNA) with and without the representative compound suggested that DNA intercalation could be their action mechanism. The 3D QSAR analysis of
N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (
6a–
r) revealed that their in vivo anti-tumor activity significantly depends on the molecular electrostatic and steric fields of the side chain of the amino acid residue. |
| doi_str_mv | 10.1016/j.bmc.2010.07.043 |
| format | Article |
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N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (
6a–
r) were synthesized as anti-tumor agents. Their IC
50 values against five human carcinoma cell lines ranged from 11.1
μM to more than 100
μM. The in vivo assay identified five derivatives of them had no anti-tumor action, the anti-tumor activity of nine derivatives of them equaled that of cytarabine, and the anti-tumor activity of three derivatives of them was higher than that of cytarabine. The UV and fluorescence spectra, as well as the relative viscosity and melting temperature measurements of calf thymus DNA (CT DNA) with and without the representative compound suggested that DNA intercalation could be their action mechanism. The 3D QSAR analysis of
N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (
6a–
r) revealed that their in vivo anti-tumor activity significantly depends on the molecular electrostatic and steric fields of the side chain of the amino acid residue.</description><identifier>ISSN: 0968-0896</identifier><identifier>EISSN: 1464-3391</identifier><identifier>DOI: 10.1016/j.bmc.2010.07.043</identifier><identifier>PMID: 20692841</identifier><language>eng</language><publisher>Amsterdam: Elsevier Ltd</publisher><subject>3D QSAR ; Amino Acids - chemical synthesis ; Amino Acids - chemistry ; Amino Acids - pharmacology ; Animals ; Anti-tumor activity ; Antineoplastic agents ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Biological and medical sciences ; Carboline ; Carbolines - chemical synthesis ; Carbolines - chemistry ; Carbolines - pharmacology ; Cattle ; Cell Line, Tumor ; Cell Proliferation ; DNA ; Docking ; General aspects ; HeLa Cells ; Humans ; Inhibitory Concentration 50 ; Intercalating Agents - chemical synthesis ; Intercalating Agents - chemistry ; Intercalating Agents - pharmacology ; Intercalation ; Medical sciences ; Mice ; Models, Molecular ; Neoplasms - drug therapy ; Neoplasms - metabolism ; Pharmacology. Drug treatments ; Quantitative Structure-Activity Relationship</subject><ispartof>Bioorganic & medicinal chemistry, 2010-09, Vol.18 (17), p.6220-6229</ispartof><rights>2010</rights><rights>2015 INIST-CNRS</rights><rights>Crown Copyright 2010. Published by Elsevier Ltd. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c382t-48527d36ca3fe7fbf57530f9879bae541b9c884061dc281d7d326f4882947d173</citedby><cites>FETCH-LOGICAL-c382t-48527d36ca3fe7fbf57530f9879bae541b9c884061dc281d7d326f4882947d173</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.bmc.2010.07.043$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,780,784,3549,27923,27924,45994</link.rule.ids><backlink>$$Uhttp://pascal-francis.inist.fr/vibad/index.php?action=getRecordDetail&idt=23195051$$DView record in Pascal Francis$$Hfree_for_read</backlink><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/20692841$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wu, Jianhui</creatorcontrib><creatorcontrib>Li, Chunyu</creatorcontrib><creatorcontrib>Zhao, Ming</creatorcontrib><creatorcontrib>Wang, Wenjing</creatorcontrib><creatorcontrib>Wang, Yuji</creatorcontrib><creatorcontrib>Peng, Shiqi</creatorcontrib><title>A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis</title><title>Bioorganic & medicinal chemistry</title><addtitle>Bioorg Med Chem</addtitle><description>Based on DOCK scores 18
N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (
6a–
r) were synthesized as anti-tumor agents. Their IC
50 values against five human carcinoma cell lines ranged from 11.1
μM to more than 100
μM. The in vivo assay identified five derivatives of them had no anti-tumor action, the anti-tumor activity of nine derivatives of them equaled that of cytarabine, and the anti-tumor activity of three derivatives of them was higher than that of cytarabine. The UV and fluorescence spectra, as well as the relative viscosity and melting temperature measurements of calf thymus DNA (CT DNA) with and without the representative compound suggested that DNA intercalation could be their action mechanism. The 3D QSAR analysis of
N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (
6a–
r) revealed that their in vivo anti-tumor activity significantly depends on the molecular electrostatic and steric fields of the side chain of the amino acid residue.</description><subject>3D QSAR</subject><subject>Amino Acids - chemical synthesis</subject><subject>Amino Acids - chemistry</subject><subject>Amino Acids - pharmacology</subject><subject>Animals</subject><subject>Anti-tumor activity</subject><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>Carboline</subject><subject>Carbolines - chemical synthesis</subject><subject>Carbolines - chemistry</subject><subject>Carbolines - pharmacology</subject><subject>Cattle</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation</subject><subject>DNA</subject><subject>Docking</subject><subject>General aspects</subject><subject>HeLa Cells</subject><subject>Humans</subject><subject>Inhibitory Concentration 50</subject><subject>Intercalating Agents - chemical synthesis</subject><subject>Intercalating Agents - chemistry</subject><subject>Intercalating Agents - pharmacology</subject><subject>Intercalation</subject><subject>Medical sciences</subject><subject>Mice</subject><subject>Models, Molecular</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - metabolism</subject><subject>Pharmacology. Drug treatments</subject><subject>Quantitative Structure-Activity Relationship</subject><issn>0968-0896</issn><issn>1464-3391</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2010</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kMtu1DAUhi1ERYfCA7BB3iA2ZOpbEpuuRuVWqRICytpynGPVo8QutmekeYK-Nh5NgB0rH-v_zq-jD6FXlKwpod3ldj3Mds1I_ZN-TQR_glZUdKLhXNGnaEVUJxsiVXeOnue8JYQwoegzdM5Ip5gUdIUeN9hOJmccHQ5xDxO2Jg1x8gGwDwWSNZMpMeX3-O4efML5EMo9ZJ_f1RzvfUkRm1B885DqloNkio9hCfdLVnZzTNjYU2TCiPkH_O3H5nudzXSobS_QmTNThpfLe4F-fvp4d_2luf36-eZ6c9tYLllphGxZP_LOGu6gd4Nr-5YTp2SvBgOtoIOyUgrS0dEyScfKss4JKZkS_Uh7foHennrrub92kIuefbYwTSZA3GXdC6lqG2OVpCfSpphzAqcfkp9NOmhK9FG_3uqqXx_1a9Lrqr_uvF7ad8MM49-NP74r8GYBTK5mXTLB-vyP41S1pD1yVycOqou9h6Sz9RAsjD6BLXqM_j9n_AYJ-KKi</recordid><startdate>20100901</startdate><enddate>20100901</enddate><creator>Wu, Jianhui</creator><creator>Li, Chunyu</creator><creator>Zhao, Ming</creator><creator>Wang, Wenjing</creator><creator>Wang, Yuji</creator><creator>Peng, Shiqi</creator><general>Elsevier Ltd</general><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>20100901</creationdate><title>A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis</title><author>Wu, Jianhui ; Li, Chunyu ; Zhao, Ming ; Wang, Wenjing ; Wang, Yuji ; Peng, Shiqi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c382t-48527d36ca3fe7fbf57530f9879bae541b9c884061dc281d7d326f4882947d173</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2010</creationdate><topic>3D QSAR</topic><topic>Amino Acids - chemical synthesis</topic><topic>Amino Acids - chemistry</topic><topic>Amino Acids - pharmacology</topic><topic>Animals</topic><topic>Anti-tumor activity</topic><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>Carboline</topic><topic>Carbolines - chemical synthesis</topic><topic>Carbolines - chemistry</topic><topic>Carbolines - pharmacology</topic><topic>Cattle</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation</topic><topic>DNA</topic><topic>Docking</topic><topic>General aspects</topic><topic>HeLa Cells</topic><topic>Humans</topic><topic>Inhibitory Concentration 50</topic><topic>Intercalating Agents - chemical synthesis</topic><topic>Intercalating Agents - chemistry</topic><topic>Intercalating Agents - pharmacology</topic><topic>Intercalation</topic><topic>Medical sciences</topic><topic>Mice</topic><topic>Models, Molecular</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - metabolism</topic><topic>Pharmacology. Drug treatments</topic><topic>Quantitative Structure-Activity Relationship</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wu, Jianhui</creatorcontrib><creatorcontrib>Li, Chunyu</creatorcontrib><creatorcontrib>Zhao, Ming</creatorcontrib><creatorcontrib>Wang, Wenjing</creatorcontrib><creatorcontrib>Wang, Yuji</creatorcontrib><creatorcontrib>Peng, Shiqi</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>Bioorganic & medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wu, Jianhui</au><au>Li, Chunyu</au><au>Zhao, Ming</au><au>Wang, Wenjing</au><au>Wang, Yuji</au><au>Peng, Shiqi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis</atitle><jtitle>Bioorganic & medicinal chemistry</jtitle><addtitle>Bioorg Med Chem</addtitle><date>2010-09-01</date><risdate>2010</risdate><volume>18</volume><issue>17</issue><spage>6220</spage><epage>6229</epage><pages>6220-6229</pages><issn>0968-0896</issn><eissn>1464-3391</eissn><abstract>Based on DOCK scores 18
N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (
6a–
r) were synthesized as anti-tumor agents. Their IC
50 values against five human carcinoma cell lines ranged from 11.1
μM to more than 100
μM. The in vivo assay identified five derivatives of them had no anti-tumor action, the anti-tumor activity of nine derivatives of them equaled that of cytarabine, and the anti-tumor activity of three derivatives of them was higher than that of cytarabine. The UV and fluorescence spectra, as well as the relative viscosity and melting temperature measurements of calf thymus DNA (CT DNA) with and without the representative compound suggested that DNA intercalation could be their action mechanism. The 3D QSAR analysis of
N-(3-benzyloxycarbonylcarboline-1-yl)ethylamino acid benzylesters (
6a–
r) revealed that their in vivo anti-tumor activity significantly depends on the molecular electrostatic and steric fields of the side chain of the amino acid residue.</abstract><cop>Amsterdam</cop><pub>Elsevier Ltd</pub><pmid>20692841</pmid><doi>10.1016/j.bmc.2010.07.043</doi><tpages>10</tpages></addata></record> |
| fulltext | fulltext |
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| ispartof | Bioorganic & medicinal chemistry, 2010-09, Vol.18 (17), p.6220-6229 |
| issn | 0968-0896 1464-3391 |
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| source | Elsevier ScienceDirect Journals Complete - AutoHoldings; MEDLINE |
| subjects | 3D QSAR Amino Acids - chemical synthesis Amino Acids - chemistry Amino Acids - pharmacology Animals Anti-tumor activity Antineoplastic agents Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Biological and medical sciences Carboline Carbolines - chemical synthesis Carbolines - chemistry Carbolines - pharmacology Cattle Cell Line, Tumor Cell Proliferation DNA Docking General aspects HeLa Cells Humans Inhibitory Concentration 50 Intercalating Agents - chemical synthesis Intercalating Agents - chemistry Intercalating Agents - pharmacology Intercalation Medical sciences Mice Models, Molecular Neoplasms - drug therapy Neoplasms - metabolism Pharmacology. Drug treatments Quantitative Structure-Activity Relationship |
| title | A class of novel carboline intercalators: Their synthesis, in vitro anti-proliferation, in vivo anti-tumor action, and 3D QSAR analysis |
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