Synthesis and biological evaluation of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position as potential antitumor agents
A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferati...
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Veröffentlicht in: | European journal of medicinal chemistry 2016-01, Vol.108, p.364-373 |
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container_title | European journal of medicinal chemistry |
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creator | Ding, Pan-Pan Gao, Man Mao, Bei-Bei Cao, Sheng-Li Liu, Cui-Huan Yang, Chao-Rui Li, Zhong-Feng Liao, Ji Zhao, Hongchang Li, Zheng Li, Jing Wang, Hailong Xu, Xingzhi |
description | A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferative activity against five cell lines, of which 5c was the most potent against HT29 cell line with an IC50 value of 5.53 μM, inducing a G2/M phase arrest in HT29 cells. Treatment of HT29 cells with 5c resulted in BubR1 phosphorylation and an increase of mitotic index in a time-dependent manner. Furthermore, 5c promoted tubulin polymerization in vitro. These results demonstrate that quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position may be potentially novel antitumor agents targeting tubulin to activate the spindle assembly checkpoint.
Compounds 5a−t were synthesized and evaluated as antitumor agents. Among them, 5c inhibited the proliferation of HT29 cells by interfering with tubulin, leading to a cell cycle arrest at G2/M phase. [Display omitted]
•Twenty dithiocarbamate derivatives of quinazolin-4(3H)-one were synthesized.•Antiproliferative activities of 5a−t against five cancer cell lines were evaluated.•Compound 5c induced a G2/M arrest in HT29 cells.•5c promoted tubulin polymerization and activated the spindle assembly checkpoint. |
doi_str_mv | 10.1016/j.ejmech.2015.11.044 |
format | Article |
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Compounds 5a−t were synthesized and evaluated as antitumor agents. Among them, 5c inhibited the proliferation of HT29 cells by interfering with tubulin, leading to a cell cycle arrest at G2/M phase. [Display omitted]
•Twenty dithiocarbamate derivatives of quinazolin-4(3H)-one were synthesized.•Antiproliferative activities of 5a−t against five cancer cell lines were evaluated.•Compound 5c induced a G2/M arrest in HT29 cells.•5c promoted tubulin polymerization and activated the spindle assembly checkpoint.</description><identifier>ISSN: 0223-5234</identifier><identifier>EISSN: 1768-3254</identifier><identifier>DOI: 10.1016/j.ejmech.2015.11.044</identifier><identifier>PMID: 26703795</identifier><language>eng</language><publisher>France: Elsevier Masson SAS</publisher><subject>Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Antiproliferative activity ; Cell Cycle - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; Dithiocarbamate ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; G2/M arrest ; Humans ; Molecular Structure ; Quinazolin-4(3H)-one ; Quinazolinones - chemical synthesis ; Quinazolinones - chemistry ; Quinazolinones - pharmacology ; Spindle assembly checkpoint ; Structure-Activity Relationship ; Synthesis ; Thiocarbamates - chemical synthesis ; Thiocarbamates - chemistry ; Thiocarbamates - pharmacology</subject><ispartof>European journal of medicinal chemistry, 2016-01, Vol.108, p.364-373</ispartof><rights>2015 Elsevier Masson SAS</rights><rights>Copyright © 2015 Elsevier Masson SAS. All rights reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c362t-bb8626af09ae56831c4912e89688a1747221fb737f44d67059483e29a94e76df3</citedby><cites>FETCH-LOGICAL-c362t-bb8626af09ae56831c4912e89688a1747221fb737f44d67059483e29a94e76df3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktohtml>$$Uhttps://www.sciencedirect.com/science/article/pii/S0223523415303809$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3537,27901,27902,65306</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/26703795$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Ding, Pan-Pan</creatorcontrib><creatorcontrib>Gao, Man</creatorcontrib><creatorcontrib>Mao, Bei-Bei</creatorcontrib><creatorcontrib>Cao, Sheng-Li</creatorcontrib><creatorcontrib>Liu, Cui-Huan</creatorcontrib><creatorcontrib>Yang, Chao-Rui</creatorcontrib><creatorcontrib>Li, Zhong-Feng</creatorcontrib><creatorcontrib>Liao, Ji</creatorcontrib><creatorcontrib>Zhao, Hongchang</creatorcontrib><creatorcontrib>Li, Zheng</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Wang, Hailong</creatorcontrib><creatorcontrib>Xu, Xingzhi</creatorcontrib><title>Synthesis and biological evaluation of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position as potential antitumor agents</title><title>European journal of medicinal chemistry</title><addtitle>Eur J Med Chem</addtitle><description>A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferative activity against five cell lines, of which 5c was the most potent against HT29 cell line with an IC50 value of 5.53 μM, inducing a G2/M phase arrest in HT29 cells. Treatment of HT29 cells with 5c resulted in BubR1 phosphorylation and an increase of mitotic index in a time-dependent manner. Furthermore, 5c promoted tubulin polymerization in vitro. These results demonstrate that quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position may be potentially novel antitumor agents targeting tubulin to activate the spindle assembly checkpoint.
Compounds 5a−t were synthesized and evaluated as antitumor agents. Among them, 5c inhibited the proliferation of HT29 cells by interfering with tubulin, leading to a cell cycle arrest at G2/M phase. [Display omitted]
•Twenty dithiocarbamate derivatives of quinazolin-4(3H)-one were synthesized.•Antiproliferative activities of 5a−t against five cancer cell lines were evaluated.•Compound 5c induced a G2/M arrest in HT29 cells.•5c promoted tubulin polymerization and activated the spindle assembly checkpoint.</description><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Antiproliferative activity</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>Dithiocarbamate</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Screening Assays, Antitumor</subject><subject>G2/M arrest</subject><subject>Humans</subject><subject>Molecular Structure</subject><subject>Quinazolin-4(3H)-one</subject><subject>Quinazolinones - chemical synthesis</subject><subject>Quinazolinones - chemistry</subject><subject>Quinazolinones - pharmacology</subject><subject>Spindle assembly checkpoint</subject><subject>Structure-Activity Relationship</subject><subject>Synthesis</subject><subject>Thiocarbamates - chemical synthesis</subject><subject>Thiocarbamates - chemistry</subject><subject>Thiocarbamates - pharmacology</subject><issn>0223-5234</issn><issn>1768-3254</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNp9kc9u1DAQhy0EokvhDRDysRwS_C9OckFCK6BIlTgAZ2viTHa9Suyt7axUnoQjz8KT4bKFI6eRRt_MTzMfIS85qznj-s2hxsOCdl8Lxpua85op9YhseKu7SopGPSYbJoSsGiHVBXmW0oEx1mjGnpILoVsm277ZkB9f7nzeY3KJgh_p4MIcds7CTPEE8wrZBU_DRG9X5-F7mJ2v1JW8fl0Fj3TE6E4FOWGiA0J0fkdHl_cuWIgDLJCRJjcitXtwnkKmW1EdQ3J_tkL69fMYMvrsShyUktclRAq70krPyZMJ5oQvHuol-fbh_dftdXXz-eOn7bubykotcjUMnRYaJtYDNrqT3KqeC-x63XXAW9UKwaehle2k1FiubnrVSRQ99ApbPU7yklyd9x5juF0xZbO4ZHGewWNYkyn_ZF3fctYXVJ1RG0NKESdzjG6BeGc4M_dOzMGcnZh7J4ZzU5yUsVcPCeuw4Phv6K-EArw9A1juPDmMJlmH3uLoItpsxuD-n_AbgA2h0A</recordid><startdate>20160127</startdate><enddate>20160127</enddate><creator>Ding, Pan-Pan</creator><creator>Gao, Man</creator><creator>Mao, Bei-Bei</creator><creator>Cao, Sheng-Li</creator><creator>Liu, Cui-Huan</creator><creator>Yang, Chao-Rui</creator><creator>Li, Zhong-Feng</creator><creator>Liao, Ji</creator><creator>Zhao, Hongchang</creator><creator>Li, Zheng</creator><creator>Li, Jing</creator><creator>Wang, Hailong</creator><creator>Xu, Xingzhi</creator><general>Elsevier Masson SAS</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></search><sort><creationdate>20160127</creationdate><title>Synthesis and biological evaluation of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position as potential antitumor agents</title><author>Ding, Pan-Pan ; Gao, Man ; Mao, Bei-Bei ; Cao, Sheng-Li ; Liu, Cui-Huan ; Yang, Chao-Rui ; Li, Zhong-Feng ; Liao, Ji ; Zhao, Hongchang ; Li, Zheng ; Li, Jing ; Wang, Hailong ; Xu, Xingzhi</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c362t-bb8626af09ae56831c4912e89688a1747221fb737f44d67059483e29a94e76df3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Antiproliferative activity</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>Dithiocarbamate</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Screening Assays, Antitumor</topic><topic>G2/M arrest</topic><topic>Humans</topic><topic>Molecular Structure</topic><topic>Quinazolin-4(3H)-one</topic><topic>Quinazolinones - chemical synthesis</topic><topic>Quinazolinones - chemistry</topic><topic>Quinazolinones - pharmacology</topic><topic>Spindle assembly checkpoint</topic><topic>Structure-Activity Relationship</topic><topic>Synthesis</topic><topic>Thiocarbamates - chemical synthesis</topic><topic>Thiocarbamates - chemistry</topic><topic>Thiocarbamates - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Ding, Pan-Pan</creatorcontrib><creatorcontrib>Gao, Man</creatorcontrib><creatorcontrib>Mao, Bei-Bei</creatorcontrib><creatorcontrib>Cao, Sheng-Li</creatorcontrib><creatorcontrib>Liu, Cui-Huan</creatorcontrib><creatorcontrib>Yang, Chao-Rui</creatorcontrib><creatorcontrib>Li, Zhong-Feng</creatorcontrib><creatorcontrib>Liao, Ji</creatorcontrib><creatorcontrib>Zhao, Hongchang</creatorcontrib><creatorcontrib>Li, Zheng</creatorcontrib><creatorcontrib>Li, Jing</creatorcontrib><creatorcontrib>Wang, Hailong</creatorcontrib><creatorcontrib>Xu, Xingzhi</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><jtitle>European journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Ding, Pan-Pan</au><au>Gao, Man</au><au>Mao, Bei-Bei</au><au>Cao, Sheng-Li</au><au>Liu, Cui-Huan</au><au>Yang, Chao-Rui</au><au>Li, Zhong-Feng</au><au>Liao, Ji</au><au>Zhao, Hongchang</au><au>Li, Zheng</au><au>Li, Jing</au><au>Wang, Hailong</au><au>Xu, Xingzhi</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Synthesis and biological evaluation of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position as potential antitumor agents</atitle><jtitle>European journal of medicinal chemistry</jtitle><addtitle>Eur J Med Chem</addtitle><date>2016-01-27</date><risdate>2016</risdate><volume>108</volume><spage>364</spage><epage>373</epage><pages>364-373</pages><issn>0223-5234</issn><eissn>1768-3254</eissn><abstract>A series of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at the C2-position were synthesized and evaluated for their antiproliferative activities against A549, MCF-7, HeLa, HT29 and HCT-116 cell lines. Most of the synthesized compounds exhibited broad spectrum antitproliferative activity against five cell lines, of which 5c was the most potent against HT29 cell line with an IC50 value of 5.53 μM, inducing a G2/M phase arrest in HT29 cells. Treatment of HT29 cells with 5c resulted in BubR1 phosphorylation and an increase of mitotic index in a time-dependent manner. Furthermore, 5c promoted tubulin polymerization in vitro. These results demonstrate that quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position may be potentially novel antitumor agents targeting tubulin to activate the spindle assembly checkpoint.
Compounds 5a−t were synthesized and evaluated as antitumor agents. Among them, 5c inhibited the proliferation of HT29 cells by interfering with tubulin, leading to a cell cycle arrest at G2/M phase. [Display omitted]
•Twenty dithiocarbamate derivatives of quinazolin-4(3H)-one were synthesized.•Antiproliferative activities of 5a−t against five cancer cell lines were evaluated.•Compound 5c induced a G2/M arrest in HT29 cells.•5c promoted tubulin polymerization and activated the spindle assembly checkpoint.</abstract><cop>France</cop><pub>Elsevier Masson SAS</pub><pmid>26703795</pmid><doi>10.1016/j.ejmech.2015.11.044</doi><tpages>10</tpages></addata></record> |
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subjects | Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Antiproliferative activity Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects Dithiocarbamate Dose-Response Relationship, Drug Drug Screening Assays, Antitumor G2/M arrest Humans Molecular Structure Quinazolin-4(3H)-one Quinazolinones - chemical synthesis Quinazolinones - chemistry Quinazolinones - pharmacology Spindle assembly checkpoint Structure-Activity Relationship Synthesis Thiocarbamates - chemical synthesis Thiocarbamates - chemistry Thiocarbamates - pharmacology |
title | Synthesis and biological evaluation of quinazolin-4(3H)-one derivatives bearing dithiocarbamate side chain at C2-position as potential antitumor agents |
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