Discovery and Optimization of N-Substituted 2-(4-pyridinyl)thiazole carboxamides against Tumor Growth through Regulating Angiogenesis Signaling Pathways
Inhibition of angiogenesis is considered as one of the desirable pathways for the treatment of tumor growth and metastasis. Herein we demonstrated that a series of pyridinyl-thiazolyl carboxamide derivatives were designed, synthesized and examined against angiogenesis through a colony formation and...
Gespeichert in:
| Veröffentlicht in: | Scientific reports 2016-09, Vol.6 (1), p.33434-33434, Article 33434 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 33434 |
|---|---|
| container_issue | 1 |
| container_start_page | 33434 |
| container_title | Scientific reports |
| container_volume | 6 |
| creator | Zhou, Wenbo Tang, Wenshu Sun, Zhenliang Li, Yunqi Dong, Yanmin Pei, Haixiang Peng, Yangrui Wang, Jinhua Shao, Ting Jiang, Zhenran Yi, Zhengfang Chen, Yihua |
| description | Inhibition of angiogenesis is considered as one of the desirable pathways for the treatment of tumor growth and metastasis. Herein we demonstrated that a series of pyridinyl-thiazolyl carboxamide derivatives were designed, synthesized and examined against angiogenesis through a colony formation and migration assays of human umbilical vein endothelial cells (HUVECs)
in vitro
. A structure-activity relationship (SAR) study was carried out and optimization toward this series of compounds resulted in the discovery of
N
-(3-methoxyphenyl)-4-methyl-2-(2-propyl-4-pyridinyl)thiazole-5-carboxamide (
3k
). The results indicated that compound
3k
showed similar or better effects compared to
Vandetanib
in suppressing HUVECs colony formation and migration as well as VEGF-induced angiogenesis in the aortic ring spreading model and chick embryo chorioallantoic membrane (CAM) model. More importantly, compound
3k
also strongly blocked tumor growth with the dosage of 30 mg/kg/day, and subsequent mechanism exploration suggested that this series of compounds took effect mainly through angiogenesis signaling pathways. Together, these results suggested compound
3k
may serve as a lead for a novel class of angiogenesis inhibitors for cancer treatments. |
| doi_str_mv | 10.1038/srep33434 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5025770</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1899083030</sourcerecordid><originalsourceid>FETCH-LOGICAL-c504t-948747d1263bbf9c2aa9fab6328a36d085af7c9ceb7cb22feb220d50aff16de83</originalsourceid><addsrcrecordid>eNplkV9P3SAYh8myZRrnxb7AQrIbNelGof-4WWKcc0uMmumuyVtKW0wLFaiufpJ93HFy9ORscgGE98nDCz-E3qfkU0pY9dk7NTGWsewV2qUkyxPKKH29td9B-97fkjhyyrOUv0U7tCwYoznfRX--ai_tvXILBtPgyynoUT9C0NZg2-KL5HqufdBhDqrBNDnIkmlxutFmGQ5Dr-HRDgpLcLX9DaNulMfQgTY-4Jt5tA6fOfsQehx6Z-euxz9VNw_Rbjp8bDptO2WU1x5f687AsDq-gtA_wOLfoTctDF7tP6176Ne305uT78n55dmPk-PzROYkCwnPqjIrm5QWrK5bLikAb6EuGK2AFQ2pcmhLyaWqS1lT2qo4kSYn0LZp0aiK7aEva-8016NqpDLBwSAmp0dwi7Cgxb8Vo3vR2XuRE5qXJYmCgyeBs3ez8kGM8UvVMIBRdvYirSjJecVTGtGP_6G3dnbx4SuKc1IxwlbCwzUlnfUx3XbTTErEKnKxiTyyH7a735DPAUfgaA34WDKdcltXvrD9BXxJuhw</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1899083030</pqid></control><display><type>article</type><title>Discovery and Optimization of N-Substituted 2-(4-pyridinyl)thiazole carboxamides against Tumor Growth through Regulating Angiogenesis Signaling Pathways</title><source>MEDLINE</source><source>DOAJ Directory of Open Access Journals</source><source>Springer Nature OA Free Journals</source><source>Nature Free</source><source>EZB-FREE-00999 freely available EZB journals</source><source>PubMed Central</source><source>Free Full-Text Journals in Chemistry</source><creator>Zhou, Wenbo ; Tang, Wenshu ; Sun, Zhenliang ; Li, Yunqi ; Dong, Yanmin ; Pei, Haixiang ; Peng, Yangrui ; Wang, Jinhua ; Shao, Ting ; Jiang, Zhenran ; Yi, Zhengfang ; Chen, Yihua</creator><creatorcontrib>Zhou, Wenbo ; Tang, Wenshu ; Sun, Zhenliang ; Li, Yunqi ; Dong, Yanmin ; Pei, Haixiang ; Peng, Yangrui ; Wang, Jinhua ; Shao, Ting ; Jiang, Zhenran ; Yi, Zhengfang ; Chen, Yihua</creatorcontrib><description>Inhibition of angiogenesis is considered as one of the desirable pathways for the treatment of tumor growth and metastasis. Herein we demonstrated that a series of pyridinyl-thiazolyl carboxamide derivatives were designed, synthesized and examined against angiogenesis through a colony formation and migration assays of human umbilical vein endothelial cells (HUVECs)
in vitro
. A structure-activity relationship (SAR) study was carried out and optimization toward this series of compounds resulted in the discovery of
N
-(3-methoxyphenyl)-4-methyl-2-(2-propyl-4-pyridinyl)thiazole-5-carboxamide (
3k
). The results indicated that compound
3k
showed similar or better effects compared to
Vandetanib
in suppressing HUVECs colony formation and migration as well as VEGF-induced angiogenesis in the aortic ring spreading model and chick embryo chorioallantoic membrane (CAM) model. More importantly, compound
3k
also strongly blocked tumor growth with the dosage of 30 mg/kg/day, and subsequent mechanism exploration suggested that this series of compounds took effect mainly through angiogenesis signaling pathways. Together, these results suggested compound
3k
may serve as a lead for a novel class of angiogenesis inhibitors for cancer treatments.</description><identifier>ISSN: 2045-2322</identifier><identifier>EISSN: 2045-2322</identifier><identifier>DOI: 10.1038/srep33434</identifier><identifier>PMID: 27633259</identifier><language>eng</language><publisher>London: Nature Publishing Group UK</publisher><subject>631/154/1435/2417 ; 631/154/309/2419 ; 96/98 ; Angiogenesis ; Angiogenesis inhibitors ; Animals ; Aorta ; Cancer ; Cell Line, Tumor ; Cell Movement - drug effects ; Cell Proliferation - drug effects ; Chick Embryo ; Chorioallantoic membrane ; Colonies ; Colony-Forming Units Assay ; Drug Design ; Drug Discovery ; Endothelial cells ; Human Umbilical Vein Endothelial Cells ; Humanities and Social Sciences ; Humans ; Male ; Metastases ; Mice, Nude ; multidisciplinary ; Neoplasms - blood supply ; Neoplasms - drug therapy ; Neoplasms - pathology ; Neovascularization, Pathologic - drug therapy ; Neovascularization, Pathologic - pathology ; Phosphorylation - drug effects ; Piperidines - pharmacology ; Piperidines - therapeutic use ; Quinazolines - pharmacology ; Quinazolines - therapeutic use ; Rats, Sprague-Dawley ; Science ; Signal Transduction ; Stress Fibers - drug effects ; Stress Fibers - metabolism ; Thiazoles - chemical synthesis ; Thiazoles - chemistry ; Thiazoles - pharmacology ; Thiazoles - therapeutic use ; Umbilical vein ; Vascular endothelial growth factor ; Wound Healing - drug effects</subject><ispartof>Scientific reports, 2016-09, Vol.6 (1), p.33434-33434, Article 33434</ispartof><rights>The Author(s) 2016</rights><rights>Copyright Nature Publishing Group Sep 2016</rights><rights>Copyright © 2016, The Author(s) 2016 The Author(s)</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c504t-948747d1263bbf9c2aa9fab6328a36d085af7c9ceb7cb22feb220d50aff16de83</citedby><cites>FETCH-LOGICAL-c504t-948747d1263bbf9c2aa9fab6328a36d085af7c9ceb7cb22feb220d50aff16de83</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025770/pdf/$$EPDF$$P50$$Gpubmedcentral$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC5025770/$$EHTML$$P50$$Gpubmedcentral$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,864,885,27924,27925,41120,42189,51576,53791,53793</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/27633259$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Zhou, Wenbo</creatorcontrib><creatorcontrib>Tang, Wenshu</creatorcontrib><creatorcontrib>Sun, Zhenliang</creatorcontrib><creatorcontrib>Li, Yunqi</creatorcontrib><creatorcontrib>Dong, Yanmin</creatorcontrib><creatorcontrib>Pei, Haixiang</creatorcontrib><creatorcontrib>Peng, Yangrui</creatorcontrib><creatorcontrib>Wang, Jinhua</creatorcontrib><creatorcontrib>Shao, Ting</creatorcontrib><creatorcontrib>Jiang, Zhenran</creatorcontrib><creatorcontrib>Yi, Zhengfang</creatorcontrib><creatorcontrib>Chen, Yihua</creatorcontrib><title>Discovery and Optimization of N-Substituted 2-(4-pyridinyl)thiazole carboxamides against Tumor Growth through Regulating Angiogenesis Signaling Pathways</title><title>Scientific reports</title><addtitle>Sci Rep</addtitle><addtitle>Sci Rep</addtitle><description>Inhibition of angiogenesis is considered as one of the desirable pathways for the treatment of tumor growth and metastasis. Herein we demonstrated that a series of pyridinyl-thiazolyl carboxamide derivatives were designed, synthesized and examined against angiogenesis through a colony formation and migration assays of human umbilical vein endothelial cells (HUVECs)
in vitro
. A structure-activity relationship (SAR) study was carried out and optimization toward this series of compounds resulted in the discovery of
N
-(3-methoxyphenyl)-4-methyl-2-(2-propyl-4-pyridinyl)thiazole-5-carboxamide (
3k
). The results indicated that compound
3k
showed similar or better effects compared to
Vandetanib
in suppressing HUVECs colony formation and migration as well as VEGF-induced angiogenesis in the aortic ring spreading model and chick embryo chorioallantoic membrane (CAM) model. More importantly, compound
3k
also strongly blocked tumor growth with the dosage of 30 mg/kg/day, and subsequent mechanism exploration suggested that this series of compounds took effect mainly through angiogenesis signaling pathways. Together, these results suggested compound
3k
may serve as a lead for a novel class of angiogenesis inhibitors for cancer treatments.</description><subject>631/154/1435/2417</subject><subject>631/154/309/2419</subject><subject>96/98</subject><subject>Angiogenesis</subject><subject>Angiogenesis inhibitors</subject><subject>Animals</subject><subject>Aorta</subject><subject>Cancer</subject><subject>Cell Line, Tumor</subject><subject>Cell Movement - drug effects</subject><subject>Cell Proliferation - drug effects</subject><subject>Chick Embryo</subject><subject>Chorioallantoic membrane</subject><subject>Colonies</subject><subject>Colony-Forming Units Assay</subject><subject>Drug Design</subject><subject>Drug Discovery</subject><subject>Endothelial cells</subject><subject>Human Umbilical Vein Endothelial Cells</subject><subject>Humanities and Social Sciences</subject><subject>Humans</subject><subject>Male</subject><subject>Metastases</subject><subject>Mice, Nude</subject><subject>multidisciplinary</subject><subject>Neoplasms - blood supply</subject><subject>Neoplasms - drug therapy</subject><subject>Neoplasms - pathology</subject><subject>Neovascularization, Pathologic - drug therapy</subject><subject>Neovascularization, Pathologic - pathology</subject><subject>Phosphorylation - drug effects</subject><subject>Piperidines - pharmacology</subject><subject>Piperidines - therapeutic use</subject><subject>Quinazolines - pharmacology</subject><subject>Quinazolines - therapeutic use</subject><subject>Rats, Sprague-Dawley</subject><subject>Science</subject><subject>Signal Transduction</subject><subject>Stress Fibers - drug effects</subject><subject>Stress Fibers - metabolism</subject><subject>Thiazoles - chemical synthesis</subject><subject>Thiazoles - chemistry</subject><subject>Thiazoles - pharmacology</subject><subject>Thiazoles - therapeutic use</subject><subject>Umbilical vein</subject><subject>Vascular endothelial growth factor</subject><subject>Wound Healing - drug effects</subject><issn>2045-2322</issn><issn>2045-2322</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2016</creationdate><recordtype>article</recordtype><sourceid>C6C</sourceid><sourceid>EIF</sourceid><sourceid>ABUWG</sourceid><sourceid>AFKRA</sourceid><sourceid>AZQEC</sourceid><sourceid>BENPR</sourceid><sourceid>CCPQU</sourceid><sourceid>DWQXO</sourceid><sourceid>GNUQQ</sourceid><recordid>eNplkV9P3SAYh8myZRrnxb7AQrIbNelGof-4WWKcc0uMmumuyVtKW0wLFaiufpJ93HFy9ORscgGE98nDCz-E3qfkU0pY9dk7NTGWsewV2qUkyxPKKH29td9B-97fkjhyyrOUv0U7tCwYoznfRX--ai_tvXILBtPgyynoUT9C0NZg2-KL5HqufdBhDqrBNDnIkmlxutFmGQ5Dr-HRDgpLcLX9DaNulMfQgTY-4Jt5tA6fOfsQehx6Z-euxz9VNw_Rbjp8bDptO2WU1x5f687AsDq-gtA_wOLfoTctDF7tP6176Ne305uT78n55dmPk-PzROYkCwnPqjIrm5QWrK5bLikAb6EuGK2AFQ2pcmhLyaWqS1lT2qo4kSYn0LZp0aiK7aEva-8016NqpDLBwSAmp0dwi7Cgxb8Vo3vR2XuRE5qXJYmCgyeBs3ez8kGM8UvVMIBRdvYirSjJecVTGtGP_6G3dnbx4SuKc1IxwlbCwzUlnfUx3XbTTErEKnKxiTyyH7a735DPAUfgaA34WDKdcltXvrD9BXxJuhw</recordid><startdate>20160916</startdate><enddate>20160916</enddate><creator>Zhou, Wenbo</creator><creator>Tang, Wenshu</creator><creator>Sun, Zhenliang</creator><creator>Li, Yunqi</creator><creator>Dong, Yanmin</creator><creator>Pei, Haixiang</creator><creator>Peng, Yangrui</creator><creator>Wang, Jinhua</creator><creator>Shao, Ting</creator><creator>Jiang, Zhenran</creator><creator>Yi, Zhengfang</creator><creator>Chen, Yihua</creator><general>Nature Publishing Group UK</general><general>Nature Publishing Group</general><scope>C6C</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>3V.</scope><scope>7X7</scope><scope>7XB</scope><scope>88A</scope><scope>88E</scope><scope>88I</scope><scope>8FE</scope><scope>8FH</scope><scope>8FI</scope><scope>8FJ</scope><scope>8FK</scope><scope>ABUWG</scope><scope>AEUYN</scope><scope>AFKRA</scope><scope>AZQEC</scope><scope>BBNVY</scope><scope>BENPR</scope><scope>BHPHI</scope><scope>CCPQU</scope><scope>DWQXO</scope><scope>FYUFA</scope><scope>GHDGH</scope><scope>GNUQQ</scope><scope>HCIFZ</scope><scope>K9.</scope><scope>LK8</scope><scope>M0S</scope><scope>M1P</scope><scope>M2P</scope><scope>M7P</scope><scope>PIMPY</scope><scope>PQEST</scope><scope>PQQKQ</scope><scope>PQUKI</scope><scope>Q9U</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20160916</creationdate><title>Discovery and Optimization of N-Substituted 2-(4-pyridinyl)thiazole carboxamides against Tumor Growth through Regulating Angiogenesis Signaling Pathways</title><author>Zhou, Wenbo ; Tang, Wenshu ; Sun, Zhenliang ; Li, Yunqi ; Dong, Yanmin ; Pei, Haixiang ; Peng, Yangrui ; Wang, Jinhua ; Shao, Ting ; Jiang, Zhenran ; Yi, Zhengfang ; Chen, Yihua</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c504t-948747d1263bbf9c2aa9fab6328a36d085af7c9ceb7cb22feb220d50aff16de83</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2016</creationdate><topic>631/154/1435/2417</topic><topic>631/154/309/2419</topic><topic>96/98</topic><topic>Angiogenesis</topic><topic>Angiogenesis inhibitors</topic><topic>Animals</topic><topic>Aorta</topic><topic>Cancer</topic><topic>Cell Line, Tumor</topic><topic>Cell Movement - drug effects</topic><topic>Cell Proliferation - drug effects</topic><topic>Chick Embryo</topic><topic>Chorioallantoic membrane</topic><topic>Colonies</topic><topic>Colony-Forming Units Assay</topic><topic>Drug Design</topic><topic>Drug Discovery</topic><topic>Endothelial cells</topic><topic>Human Umbilical Vein Endothelial Cells</topic><topic>Humanities and Social Sciences</topic><topic>Humans</topic><topic>Male</topic><topic>Metastases</topic><topic>Mice, Nude</topic><topic>multidisciplinary</topic><topic>Neoplasms - blood supply</topic><topic>Neoplasms - drug therapy</topic><topic>Neoplasms - pathology</topic><topic>Neovascularization, Pathologic - drug therapy</topic><topic>Neovascularization, Pathologic - pathology</topic><topic>Phosphorylation - drug effects</topic><topic>Piperidines - pharmacology</topic><topic>Piperidines - therapeutic use</topic><topic>Quinazolines - pharmacology</topic><topic>Quinazolines - therapeutic use</topic><topic>Rats, Sprague-Dawley</topic><topic>Science</topic><topic>Signal Transduction</topic><topic>Stress Fibers - drug effects</topic><topic>Stress Fibers - metabolism</topic><topic>Thiazoles - chemical synthesis</topic><topic>Thiazoles - chemistry</topic><topic>Thiazoles - pharmacology</topic><topic>Thiazoles - therapeutic use</topic><topic>Umbilical vein</topic><topic>Vascular endothelial growth factor</topic><topic>Wound Healing - drug effects</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Zhou, Wenbo</creatorcontrib><creatorcontrib>Tang, Wenshu</creatorcontrib><creatorcontrib>Sun, Zhenliang</creatorcontrib><creatorcontrib>Li, Yunqi</creatorcontrib><creatorcontrib>Dong, Yanmin</creatorcontrib><creatorcontrib>Pei, Haixiang</creatorcontrib><creatorcontrib>Peng, Yangrui</creatorcontrib><creatorcontrib>Wang, Jinhua</creatorcontrib><creatorcontrib>Shao, Ting</creatorcontrib><creatorcontrib>Jiang, Zhenran</creatorcontrib><creatorcontrib>Yi, Zhengfang</creatorcontrib><creatorcontrib>Chen, Yihua</creatorcontrib><collection>Springer Nature OA Free Journals</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>ProQuest Central (Corporate)</collection><collection>Health & Medical Collection</collection><collection>ProQuest Central (purchase pre-March 2016)</collection><collection>Biology Database (Alumni Edition)</collection><collection>Medical Database (Alumni Edition)</collection><collection>Science Database (Alumni Edition)</collection><collection>ProQuest SciTech Collection</collection><collection>ProQuest Natural Science Collection</collection><collection>Hospital Premium Collection</collection><collection>Hospital Premium Collection (Alumni Edition)</collection><collection>ProQuest Central (Alumni) (purchase pre-March 2016)</collection><collection>ProQuest Central (Alumni Edition)</collection><collection>ProQuest One Sustainability</collection><collection>ProQuest Central UK/Ireland</collection><collection>ProQuest Central Essentials</collection><collection>Biological Science Collection</collection><collection>ProQuest Central</collection><collection>Natural Science Collection</collection><collection>ProQuest One Community College</collection><collection>ProQuest Central Korea</collection><collection>Health Research Premium Collection</collection><collection>Health Research Premium Collection (Alumni)</collection><collection>ProQuest Central Student</collection><collection>SciTech Premium Collection</collection><collection>ProQuest Health & Medical Complete (Alumni)</collection><collection>ProQuest Biological Science Collection</collection><collection>Health & Medical Collection (Alumni Edition)</collection><collection>Medical Database</collection><collection>Science Database</collection><collection>Biological Science Database</collection><collection>Publicly Available Content Database</collection><collection>ProQuest One Academic Eastern Edition (DO NOT USE)</collection><collection>ProQuest One Academic</collection><collection>ProQuest One Academic UKI Edition</collection><collection>ProQuest Central Basic</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Scientific reports</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Zhou, Wenbo</au><au>Tang, Wenshu</au><au>Sun, Zhenliang</au><au>Li, Yunqi</au><au>Dong, Yanmin</au><au>Pei, Haixiang</au><au>Peng, Yangrui</au><au>Wang, Jinhua</au><au>Shao, Ting</au><au>Jiang, Zhenran</au><au>Yi, Zhengfang</au><au>Chen, Yihua</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Discovery and Optimization of N-Substituted 2-(4-pyridinyl)thiazole carboxamides against Tumor Growth through Regulating Angiogenesis Signaling Pathways</atitle><jtitle>Scientific reports</jtitle><stitle>Sci Rep</stitle><addtitle>Sci Rep</addtitle><date>2016-09-16</date><risdate>2016</risdate><volume>6</volume><issue>1</issue><spage>33434</spage><epage>33434</epage><pages>33434-33434</pages><artnum>33434</artnum><issn>2045-2322</issn><eissn>2045-2322</eissn><abstract>Inhibition of angiogenesis is considered as one of the desirable pathways for the treatment of tumor growth and metastasis. Herein we demonstrated that a series of pyridinyl-thiazolyl carboxamide derivatives were designed, synthesized and examined against angiogenesis through a colony formation and migration assays of human umbilical vein endothelial cells (HUVECs)
in vitro
. A structure-activity relationship (SAR) study was carried out and optimization toward this series of compounds resulted in the discovery of
N
-(3-methoxyphenyl)-4-methyl-2-(2-propyl-4-pyridinyl)thiazole-5-carboxamide (
3k
). The results indicated that compound
3k
showed similar or better effects compared to
Vandetanib
in suppressing HUVECs colony formation and migration as well as VEGF-induced angiogenesis in the aortic ring spreading model and chick embryo chorioallantoic membrane (CAM) model. More importantly, compound
3k
also strongly blocked tumor growth with the dosage of 30 mg/kg/day, and subsequent mechanism exploration suggested that this series of compounds took effect mainly through angiogenesis signaling pathways. Together, these results suggested compound
3k
may serve as a lead for a novel class of angiogenesis inhibitors for cancer treatments.</abstract><cop>London</cop><pub>Nature Publishing Group UK</pub><pmid>27633259</pmid><doi>10.1038/srep33434</doi><tpages>1</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 2045-2322 |
| ispartof | Scientific reports, 2016-09, Vol.6 (1), p.33434-33434, Article 33434 |
| issn | 2045-2322 2045-2322 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_5025770 |
| source | MEDLINE; DOAJ Directory of Open Access Journals; Springer Nature OA Free Journals; Nature Free; EZB-FREE-00999 freely available EZB journals; PubMed Central; Free Full-Text Journals in Chemistry |
| subjects | 631/154/1435/2417 631/154/309/2419 96/98 Angiogenesis Angiogenesis inhibitors Animals Aorta Cancer Cell Line, Tumor Cell Movement - drug effects Cell Proliferation - drug effects Chick Embryo Chorioallantoic membrane Colonies Colony-Forming Units Assay Drug Design Drug Discovery Endothelial cells Human Umbilical Vein Endothelial Cells Humanities and Social Sciences Humans Male Metastases Mice, Nude multidisciplinary Neoplasms - blood supply Neoplasms - drug therapy Neoplasms - pathology Neovascularization, Pathologic - drug therapy Neovascularization, Pathologic - pathology Phosphorylation - drug effects Piperidines - pharmacology Piperidines - therapeutic use Quinazolines - pharmacology Quinazolines - therapeutic use Rats, Sprague-Dawley Science Signal Transduction Stress Fibers - drug effects Stress Fibers - metabolism Thiazoles - chemical synthesis Thiazoles - chemistry Thiazoles - pharmacology Thiazoles - therapeutic use Umbilical vein Vascular endothelial growth factor Wound Healing - drug effects |
| title | Discovery and Optimization of N-Substituted 2-(4-pyridinyl)thiazole carboxamides against Tumor Growth through Regulating Angiogenesis Signaling Pathways |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2025-01-08T01%3A42%3A00IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-proquest_pubme&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=Discovery%20and%20Optimization%20of%20N-Substituted%202-(4-pyridinyl)thiazole%20carboxamides%20against%20Tumor%20Growth%20through%20Regulating%20Angiogenesis%20Signaling%20Pathways&rft.jtitle=Scientific%20reports&rft.au=Zhou,%20Wenbo&rft.date=2016-09-16&rft.volume=6&rft.issue=1&rft.spage=33434&rft.epage=33434&rft.pages=33434-33434&rft.artnum=33434&rft.issn=2045-2322&rft.eissn=2045-2322&rft_id=info:doi/10.1038/srep33434&rft_dat=%3Cproquest_pubme%3E1899083030%3C/proquest_pubme%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_pqid=1899083030&rft_id=info:pmid/27633259&rfr_iscdi=true |