Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20(S)‑Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents
Twelve novel 20-sulfonylamidine derivatives (9a–9l) of camptothecin (1) were synthesized via a Cu-catalyzed three-component reaction. They showed similar or superior cytotoxicity compared with that of irinotecan (3) against A-549, DU-145, KB, and multidrug-resistant (MDR) KBvin tumor cell lines. Com...
Gespeichert in:
| Veröffentlicht in: | Journal of medicinal chemistry 2014-07, Vol.57 (14), p.6008-6018 |
|---|---|
| Hauptverfasser: | , , , , , , , , , , , , , , , , , , , , |
| Format: | Artikel |
| Sprache: | eng |
| Schlagworte: | |
| Online-Zugang: | Volltext |
| Tags: |
Tag hinzufügen
Keine Tags, Fügen Sie den ersten Tag hinzu!
|
| container_end_page | 6018 |
|---|---|
| container_issue | 14 |
| container_start_page | 6008 |
| container_title | Journal of medicinal chemistry |
| container_volume | 57 |
| creator | Wang, Mei-Juan Liu, Ying-Qian Chang, Ling-Chu Wang, Chih-Ya Zhao, Yong-Long Zhao, Xiao-Bo Qian, Keduo Nan, Xiang Yang, Liu Yang, Xiao-Ming Hung, Hsin-Yi Yang, Jai-Sing Kuo, Daih-Huang Goto, Masuo Morris-Natschke, Susan L Pan, Shiow-Lin Teng, Che-Ming Kuo, Sheng-Chu Wu, Tian-Shung Wu, Yang-Chang Lee, Kuo-Hsiung |
| description | Twelve novel 20-sulfonylamidine derivatives (9a–9l) of camptothecin (1) were synthesized via a Cu-catalyzed three-component reaction. They showed similar or superior cytotoxicity compared with that of irinotecan (3) against A-549, DU-145, KB, and multidrug-resistant (MDR) KBvin tumor cell lines. Compound 9a demonstrated better cytotoxicity against MDR cells compared with that of 1 and 3. Mechanistically, 9a induced significant DNA damage by selectively inhibiting Topoisomerase (Topo) I and activating the ATM/Chk related DNA damage-response pathway. In xenograft models, 9a demonstrated significant activity without overt adverse effects at 5 and 10 mg/kg, comparable to 3 at 100 mg/kg. Notably, 9a at 300 mg/kg (i.p.) showed no overt toxicity in contrast to 1 (LD50 56.2 mg/kg, i.p.) and 3 (LD50 177.5 mg/kg, i.p.). Intact 9a inhibited Topo I activity in a cell-free assay in a manner similar to that of 1, confirming that 9a is a new class of Topo I inhibitor. 20-Sulfonylamidine 1-derivative 9a merits development as an anticancer clinical trial candidate. |
| doi_str_mv | 10.1021/jm5003588 |
| format | Article |
| fullrecord | <record><control><sourceid>proquest_pubme</sourceid><recordid>TN_cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4111373</recordid><sourceformat>XML</sourceformat><sourcesystem>PC</sourcesystem><sourcerecordid>1701488372</sourcerecordid><originalsourceid>FETCH-LOGICAL-a504t-3ba1f3883cbf4ceaccfd2aecba751c26b9360bf870ebf34a744ea08c09d7927a3</originalsourceid><addsrcrecordid>eNptkctuEzEUhi0EoqGw4AWQN0it1AHfJjOzQYrScpHKRUpZW2c8duJoxk5tT0R2vEAXvCJPgkNKBBIr3z59_5F_hJ5T8ooSRl-vh5IQXtb1AzShJSOFqIl4iCaEMFawKeMn6EmMa5IhyvhjdML2fNOUE3R3qaNdugu82Lm0yvt4gT9qtQJn4xCxN3imkvUZANfhG__NKpt2-_tPfqt7zMjZ4vzn9x-LsTfe7XoYbGedxpc62C0ku9W_JXMYNsnnAGUdhoi_-KRdwjOXbBoHH_Bsmc_xKXpkoI_62f16ir6-vbqZvy-uP7_7MJ9dF1ASkQreAjW8rrlqjVAalDIdA61aqEqq2LRt-JS0pq6Ibg0XUAmhgdSKNF3VsAr4KXpz8G7GdtCdytkBerkJdoCwkx6s_PfF2ZVc-q0UlFJe8Sw4uxcEfzvqmORgo9J9D077MUpaESrygBXL6PkBVcHHGLQ5xlAi9_XJY32ZffH3XEfyT18ZeHkAQEW59mNw-Zv-I_oFOeulLA</addsrcrecordid><sourcetype>Open Access Repository</sourcetype><iscdi>true</iscdi><recordtype>article</recordtype><pqid>1701488372</pqid></control><display><type>article</type><title>Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20(S)‑Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents</title><source>MEDLINE</source><source>American Chemical Society Journals</source><creator>Wang, Mei-Juan ; Liu, Ying-Qian ; Chang, Ling-Chu ; Wang, Chih-Ya ; Zhao, Yong-Long ; Zhao, Xiao-Bo ; Qian, Keduo ; Nan, Xiang ; Yang, Liu ; Yang, Xiao-Ming ; Hung, Hsin-Yi ; Yang, Jai-Sing ; Kuo, Daih-Huang ; Goto, Masuo ; Morris-Natschke, Susan L ; Pan, Shiow-Lin ; Teng, Che-Ming ; Kuo, Sheng-Chu ; Wu, Tian-Shung ; Wu, Yang-Chang ; Lee, Kuo-Hsiung</creator><creatorcontrib>Wang, Mei-Juan ; Liu, Ying-Qian ; Chang, Ling-Chu ; Wang, Chih-Ya ; Zhao, Yong-Long ; Zhao, Xiao-Bo ; Qian, Keduo ; Nan, Xiang ; Yang, Liu ; Yang, Xiao-Ming ; Hung, Hsin-Yi ; Yang, Jai-Sing ; Kuo, Daih-Huang ; Goto, Masuo ; Morris-Natschke, Susan L ; Pan, Shiow-Lin ; Teng, Che-Ming ; Kuo, Sheng-Chu ; Wu, Tian-Shung ; Wu, Yang-Chang ; Lee, Kuo-Hsiung</creatorcontrib><description>Twelve novel 20-sulfonylamidine derivatives (9a–9l) of camptothecin (1) were synthesized via a Cu-catalyzed three-component reaction. They showed similar or superior cytotoxicity compared with that of irinotecan (3) against A-549, DU-145, KB, and multidrug-resistant (MDR) KBvin tumor cell lines. Compound 9a demonstrated better cytotoxicity against MDR cells compared with that of 1 and 3. Mechanistically, 9a induced significant DNA damage by selectively inhibiting Topoisomerase (Topo) I and activating the ATM/Chk related DNA damage-response pathway. In xenograft models, 9a demonstrated significant activity without overt adverse effects at 5 and 10 mg/kg, comparable to 3 at 100 mg/kg. Notably, 9a at 300 mg/kg (i.p.) showed no overt toxicity in contrast to 1 (LD50 56.2 mg/kg, i.p.) and 3 (LD50 177.5 mg/kg, i.p.). Intact 9a inhibited Topo I activity in a cell-free assay in a manner similar to that of 1, confirming that 9a is a new class of Topo I inhibitor. 20-Sulfonylamidine 1-derivative 9a merits development as an anticancer clinical trial candidate.</description><identifier>ISSN: 0022-2623</identifier><identifier>EISSN: 1520-4804</identifier><identifier>DOI: 10.1021/jm5003588</identifier><identifier>PMID: 25003995</identifier><language>eng</language><publisher>United States: American Chemical Society</publisher><subject>Amidines - chemistry ; Animals ; Antineoplastic Agents - chemical synthesis ; Antineoplastic Agents - chemistry ; Antineoplastic Agents - pharmacology ; Apoptosis - drug effects ; Camptothecin - analogs & derivatives ; Camptothecin - chemistry ; Cell Cycle - drug effects ; Cell Line, Tumor ; Cell Proliferation - drug effects ; DNA Topoisomerases, Type I - metabolism ; Dose-Response Relationship, Drug ; Drug Design ; Drug Screening Assays, Antitumor ; Female ; HCT116 Cells ; Humans ; KB Cells ; Mice ; Mice, Inbred BALB C ; Mice, Nude ; Molecular Conformation ; Neoplasms, Experimental - drug therapy ; Neoplasms, Experimental - pathology ; Structure-Activity Relationship ; Sulfonamides - chemistry ; Topoisomerase I Inhibitors - chemical synthesis ; Topoisomerase I Inhibitors - chemistry ; Topoisomerase I Inhibitors - pharmacology</subject><ispartof>Journal of medicinal chemistry, 2014-07, Vol.57 (14), p.6008-6018</ispartof><rights>Copyright © 2014 American Chemical Society</rights><rights>Copyright © 2014 American Chemical Society 2014 American Chemical Society</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-a504t-3ba1f3883cbf4ceaccfd2aecba751c26b9360bf870ebf34a744ea08c09d7927a3</citedby><cites>FETCH-LOGICAL-a504t-3ba1f3883cbf4ceaccfd2aecba751c26b9360bf870ebf34a744ea08c09d7927a3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://pubs.acs.org/doi/pdf/10.1021/jm5003588$$EPDF$$P50$$Gacs$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://pubs.acs.org/doi/10.1021/jm5003588$$EHTML$$P50$$Gacs$$Hfree_for_read</linktohtml><link.rule.ids>230,314,780,784,885,2765,27076,27924,27925,56738,56788</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/25003995$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Wang, Mei-Juan</creatorcontrib><creatorcontrib>Liu, Ying-Qian</creatorcontrib><creatorcontrib>Chang, Ling-Chu</creatorcontrib><creatorcontrib>Wang, Chih-Ya</creatorcontrib><creatorcontrib>Zhao, Yong-Long</creatorcontrib><creatorcontrib>Zhao, Xiao-Bo</creatorcontrib><creatorcontrib>Qian, Keduo</creatorcontrib><creatorcontrib>Nan, Xiang</creatorcontrib><creatorcontrib>Yang, Liu</creatorcontrib><creatorcontrib>Yang, Xiao-Ming</creatorcontrib><creatorcontrib>Hung, Hsin-Yi</creatorcontrib><creatorcontrib>Yang, Jai-Sing</creatorcontrib><creatorcontrib>Kuo, Daih-Huang</creatorcontrib><creatorcontrib>Goto, Masuo</creatorcontrib><creatorcontrib>Morris-Natschke, Susan L</creatorcontrib><creatorcontrib>Pan, Shiow-Lin</creatorcontrib><creatorcontrib>Teng, Che-Ming</creatorcontrib><creatorcontrib>Kuo, Sheng-Chu</creatorcontrib><creatorcontrib>Wu, Tian-Shung</creatorcontrib><creatorcontrib>Wu, Yang-Chang</creatorcontrib><creatorcontrib>Lee, Kuo-Hsiung</creatorcontrib><title>Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20(S)‑Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents</title><title>Journal of medicinal chemistry</title><addtitle>J. Med. Chem</addtitle><description>Twelve novel 20-sulfonylamidine derivatives (9a–9l) of camptothecin (1) were synthesized via a Cu-catalyzed three-component reaction. They showed similar or superior cytotoxicity compared with that of irinotecan (3) against A-549, DU-145, KB, and multidrug-resistant (MDR) KBvin tumor cell lines. Compound 9a demonstrated better cytotoxicity against MDR cells compared with that of 1 and 3. Mechanistically, 9a induced significant DNA damage by selectively inhibiting Topoisomerase (Topo) I and activating the ATM/Chk related DNA damage-response pathway. In xenograft models, 9a demonstrated significant activity without overt adverse effects at 5 and 10 mg/kg, comparable to 3 at 100 mg/kg. Notably, 9a at 300 mg/kg (i.p.) showed no overt toxicity in contrast to 1 (LD50 56.2 mg/kg, i.p.) and 3 (LD50 177.5 mg/kg, i.p.). Intact 9a inhibited Topo I activity in a cell-free assay in a manner similar to that of 1, confirming that 9a is a new class of Topo I inhibitor. 20-Sulfonylamidine 1-derivative 9a merits development as an anticancer clinical trial candidate.</description><subject>Amidines - chemistry</subject><subject>Animals</subject><subject>Antineoplastic Agents - chemical synthesis</subject><subject>Antineoplastic Agents - chemistry</subject><subject>Antineoplastic Agents - pharmacology</subject><subject>Apoptosis - drug effects</subject><subject>Camptothecin - analogs & derivatives</subject><subject>Camptothecin - chemistry</subject><subject>Cell Cycle - drug effects</subject><subject>Cell Line, Tumor</subject><subject>Cell Proliferation - drug effects</subject><subject>DNA Topoisomerases, Type I - metabolism</subject><subject>Dose-Response Relationship, Drug</subject><subject>Drug Design</subject><subject>Drug Screening Assays, Antitumor</subject><subject>Female</subject><subject>HCT116 Cells</subject><subject>Humans</subject><subject>KB Cells</subject><subject>Mice</subject><subject>Mice, Inbred BALB C</subject><subject>Mice, Nude</subject><subject>Molecular Conformation</subject><subject>Neoplasms, Experimental - drug therapy</subject><subject>Neoplasms, Experimental - pathology</subject><subject>Structure-Activity Relationship</subject><subject>Sulfonamides - chemistry</subject><subject>Topoisomerase I Inhibitors - chemical synthesis</subject><subject>Topoisomerase I Inhibitors - chemistry</subject><subject>Topoisomerase I Inhibitors - pharmacology</subject><issn>0022-2623</issn><issn>1520-4804</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2014</creationdate><recordtype>article</recordtype><sourceid>N~.</sourceid><sourceid>EIF</sourceid><recordid>eNptkctuEzEUhi0EoqGw4AWQN0it1AHfJjOzQYrScpHKRUpZW2c8duJoxk5tT0R2vEAXvCJPgkNKBBIr3z59_5F_hJ5T8ooSRl-vh5IQXtb1AzShJSOFqIl4iCaEMFawKeMn6EmMa5IhyvhjdML2fNOUE3R3qaNdugu82Lm0yvt4gT9qtQJn4xCxN3imkvUZANfhG__NKpt2-_tPfqt7zMjZ4vzn9x-LsTfe7XoYbGedxpc62C0ku9W_JXMYNsnnAGUdhoi_-KRdwjOXbBoHH_Bsmc_xKXpkoI_62f16ir6-vbqZvy-uP7_7MJ9dF1ASkQreAjW8rrlqjVAalDIdA61aqEqq2LRt-JS0pq6Ibg0XUAmhgdSKNF3VsAr4KXpz8G7GdtCdytkBerkJdoCwkx6s_PfF2ZVc-q0UlFJe8Sw4uxcEfzvqmORgo9J9D077MUpaESrygBXL6PkBVcHHGLQ5xlAi9_XJY32ZffH3XEfyT18ZeHkAQEW59mNw-Zv-I_oFOeulLA</recordid><startdate>20140724</startdate><enddate>20140724</enddate><creator>Wang, Mei-Juan</creator><creator>Liu, Ying-Qian</creator><creator>Chang, Ling-Chu</creator><creator>Wang, Chih-Ya</creator><creator>Zhao, Yong-Long</creator><creator>Zhao, Xiao-Bo</creator><creator>Qian, Keduo</creator><creator>Nan, Xiang</creator><creator>Yang, Liu</creator><creator>Yang, Xiao-Ming</creator><creator>Hung, Hsin-Yi</creator><creator>Yang, Jai-Sing</creator><creator>Kuo, Daih-Huang</creator><creator>Goto, Masuo</creator><creator>Morris-Natschke, Susan L</creator><creator>Pan, Shiow-Lin</creator><creator>Teng, Che-Ming</creator><creator>Kuo, Sheng-Chu</creator><creator>Wu, Tian-Shung</creator><creator>Wu, Yang-Chang</creator><creator>Lee, Kuo-Hsiung</creator><general>American Chemical Society</general><scope>N~.</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>7QO</scope><scope>8FD</scope><scope>FR3</scope><scope>P64</scope><scope>5PM</scope></search><sort><creationdate>20140724</creationdate><title>Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20(S)‑Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents</title><author>Wang, Mei-Juan ; Liu, Ying-Qian ; Chang, Ling-Chu ; Wang, Chih-Ya ; Zhao, Yong-Long ; Zhao, Xiao-Bo ; Qian, Keduo ; Nan, Xiang ; Yang, Liu ; Yang, Xiao-Ming ; Hung, Hsin-Yi ; Yang, Jai-Sing ; Kuo, Daih-Huang ; Goto, Masuo ; Morris-Natschke, Susan L ; Pan, Shiow-Lin ; Teng, Che-Ming ; Kuo, Sheng-Chu ; Wu, Tian-Shung ; Wu, Yang-Chang ; Lee, Kuo-Hsiung</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-a504t-3ba1f3883cbf4ceaccfd2aecba751c26b9360bf870ebf34a744ea08c09d7927a3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2014</creationdate><topic>Amidines - chemistry</topic><topic>Animals</topic><topic>Antineoplastic Agents - chemical synthesis</topic><topic>Antineoplastic Agents - chemistry</topic><topic>Antineoplastic Agents - pharmacology</topic><topic>Apoptosis - drug effects</topic><topic>Camptothecin - analogs & derivatives</topic><topic>Camptothecin - chemistry</topic><topic>Cell Cycle - drug effects</topic><topic>Cell Line, Tumor</topic><topic>Cell Proliferation - drug effects</topic><topic>DNA Topoisomerases, Type I - metabolism</topic><topic>Dose-Response Relationship, Drug</topic><topic>Drug Design</topic><topic>Drug Screening Assays, Antitumor</topic><topic>Female</topic><topic>HCT116 Cells</topic><topic>Humans</topic><topic>KB Cells</topic><topic>Mice</topic><topic>Mice, Inbred BALB C</topic><topic>Mice, Nude</topic><topic>Molecular Conformation</topic><topic>Neoplasms, Experimental - drug therapy</topic><topic>Neoplasms, Experimental - pathology</topic><topic>Structure-Activity Relationship</topic><topic>Sulfonamides - chemistry</topic><topic>Topoisomerase I Inhibitors - chemical synthesis</topic><topic>Topoisomerase I Inhibitors - chemistry</topic><topic>Topoisomerase I Inhibitors - pharmacology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Wang, Mei-Juan</creatorcontrib><creatorcontrib>Liu, Ying-Qian</creatorcontrib><creatorcontrib>Chang, Ling-Chu</creatorcontrib><creatorcontrib>Wang, Chih-Ya</creatorcontrib><creatorcontrib>Zhao, Yong-Long</creatorcontrib><creatorcontrib>Zhao, Xiao-Bo</creatorcontrib><creatorcontrib>Qian, Keduo</creatorcontrib><creatorcontrib>Nan, Xiang</creatorcontrib><creatorcontrib>Yang, Liu</creatorcontrib><creatorcontrib>Yang, Xiao-Ming</creatorcontrib><creatorcontrib>Hung, Hsin-Yi</creatorcontrib><creatorcontrib>Yang, Jai-Sing</creatorcontrib><creatorcontrib>Kuo, Daih-Huang</creatorcontrib><creatorcontrib>Goto, Masuo</creatorcontrib><creatorcontrib>Morris-Natschke, Susan L</creatorcontrib><creatorcontrib>Pan, Shiow-Lin</creatorcontrib><creatorcontrib>Teng, Che-Ming</creatorcontrib><creatorcontrib>Kuo, Sheng-Chu</creatorcontrib><creatorcontrib>Wu, Tian-Shung</creatorcontrib><creatorcontrib>Wu, Yang-Chang</creatorcontrib><creatorcontrib>Lee, Kuo-Hsiung</creatorcontrib><collection>American Chemical Society (ACS) Open Access</collection><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>Biotechnology Research Abstracts</collection><collection>Technology Research Database</collection><collection>Engineering Research Database</collection><collection>Biotechnology and BioEngineering Abstracts</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of medicinal chemistry</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Wang, Mei-Juan</au><au>Liu, Ying-Qian</au><au>Chang, Ling-Chu</au><au>Wang, Chih-Ya</au><au>Zhao, Yong-Long</au><au>Zhao, Xiao-Bo</au><au>Qian, Keduo</au><au>Nan, Xiang</au><au>Yang, Liu</au><au>Yang, Xiao-Ming</au><au>Hung, Hsin-Yi</au><au>Yang, Jai-Sing</au><au>Kuo, Daih-Huang</au><au>Goto, Masuo</au><au>Morris-Natschke, Susan L</au><au>Pan, Shiow-Lin</au><au>Teng, Che-Ming</au><au>Kuo, Sheng-Chu</au><au>Wu, Tian-Shung</au><au>Wu, Yang-Chang</au><au>Lee, Kuo-Hsiung</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20(S)‑Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents</atitle><jtitle>Journal of medicinal chemistry</jtitle><addtitle>J. Med. Chem</addtitle><date>2014-07-24</date><risdate>2014</risdate><volume>57</volume><issue>14</issue><spage>6008</spage><epage>6018</epage><pages>6008-6018</pages><issn>0022-2623</issn><eissn>1520-4804</eissn><abstract>Twelve novel 20-sulfonylamidine derivatives (9a–9l) of camptothecin (1) were synthesized via a Cu-catalyzed three-component reaction. They showed similar or superior cytotoxicity compared with that of irinotecan (3) against A-549, DU-145, KB, and multidrug-resistant (MDR) KBvin tumor cell lines. Compound 9a demonstrated better cytotoxicity against MDR cells compared with that of 1 and 3. Mechanistically, 9a induced significant DNA damage by selectively inhibiting Topoisomerase (Topo) I and activating the ATM/Chk related DNA damage-response pathway. In xenograft models, 9a demonstrated significant activity without overt adverse effects at 5 and 10 mg/kg, comparable to 3 at 100 mg/kg. Notably, 9a at 300 mg/kg (i.p.) showed no overt toxicity in contrast to 1 (LD50 56.2 mg/kg, i.p.) and 3 (LD50 177.5 mg/kg, i.p.). Intact 9a inhibited Topo I activity in a cell-free assay in a manner similar to that of 1, confirming that 9a is a new class of Topo I inhibitor. 20-Sulfonylamidine 1-derivative 9a merits development as an anticancer clinical trial candidate.</abstract><cop>United States</cop><pub>American Chemical Society</pub><pmid>25003995</pmid><doi>10.1021/jm5003588</doi><tpages>11</tpages><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0022-2623 |
| ispartof | Journal of medicinal chemistry, 2014-07, Vol.57 (14), p.6008-6018 |
| issn | 0022-2623 1520-4804 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_4111373 |
| source | MEDLINE; American Chemical Society Journals |
| subjects | Amidines - chemistry Animals Antineoplastic Agents - chemical synthesis Antineoplastic Agents - chemistry Antineoplastic Agents - pharmacology Apoptosis - drug effects Camptothecin - analogs & derivatives Camptothecin - chemistry Cell Cycle - drug effects Cell Line, Tumor Cell Proliferation - drug effects DNA Topoisomerases, Type I - metabolism Dose-Response Relationship, Drug Drug Design Drug Screening Assays, Antitumor Female HCT116 Cells Humans KB Cells Mice Mice, Inbred BALB C Mice, Nude Molecular Conformation Neoplasms, Experimental - drug therapy Neoplasms, Experimental - pathology Structure-Activity Relationship Sulfonamides - chemistry Topoisomerase I Inhibitors - chemical synthesis Topoisomerase I Inhibitors - chemistry Topoisomerase I Inhibitors - pharmacology |
| title | Design, Synthesis, Mechanisms of Action, and Toxicity of Novel 20(S)‑Sulfonylamidine Derivatives of Camptothecin as Potent Antitumor Agents |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-21T16%3A41%3A30IST&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=Design,%20Synthesis,%20Mechanisms%20of%20Action,%20and%20Toxicity%20of%20Novel%2020(S)%E2%80%91Sulfonylamidine%20Derivatives%20of%20Camptothecin%20as%20Potent%20Antitumor%20Agents&rft.jtitle=Journal%20of%20medicinal%20chemistry&rft.au=Wang,%20Mei-Juan&rft.date=2014-07-24&rft.volume=57&rft.issue=14&rft.spage=6008&rft.epage=6018&rft.pages=6008-6018&rft.issn=0022-2623&rft.eissn=1520-4804&rft_id=info:doi/10.1021/jm5003588&rft_dat=%3Cproquest_pubme%3E1701488372%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=1701488372&rft_id=info:pmid/25003995&rfr_iscdi=true |