Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents
Herein we discovered a new series of phthalazinone acridine derivatives as PARP and Topo dual inhibitors, with compound 9a exhibited broad antiproliferative activities and induced remarkable apoptosis and S cell cycle arrest in HCT116 cells. [Display omitted] In this study, we designed and synthesiz...
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| Veröffentlicht in: | Chinese chemical letters 2020-02, Vol.31 (2), p.404-408 |
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| creator | Dai, Qiuzi Chen, Jiwei Gao, Chunmei Sun, Qinsheng Yuan, Zigao Jiang, Yuyang |
| description | Herein we discovered a new series of phthalazinone acridine derivatives as PARP and Topo dual inhibitors, with compound 9a exhibited broad antiproliferative activities and induced remarkable apoptosis and S cell cycle arrest in HCT116 cells.
[Display omitted]
In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy. |
| doi_str_mv | 10.1016/j.cclet.2019.06.019 |
| format | Article |
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[Display omitted]
In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.</description><identifier>ISSN: 1001-8417</identifier><identifier>EISSN: 1878-5964</identifier><identifier>DOI: 10.1016/j.cclet.2019.06.019</identifier><language>eng</language><publisher>Elsevier B.V</publisher><subject>Acridines ; Antitumor bioactivity ; Multitarget ; PARP ; Topo</subject><ispartof>Chinese chemical letters, 2020-02, Vol.31 (2), p.404-408</ispartof><rights>2020 The Author</rights><rights>Copyright © Wanfang Data Co. Ltd. All Rights Reserved.</rights><lds50>peer_reviewed</lds50><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c335t-e8a381ca196b223059a66e09debf7d274df768492871a783ee31530285330def3</citedby><cites>FETCH-LOGICAL-c335t-e8a381ca196b223059a66e09debf7d274df768492871a783ee31530285330def3</cites><orcidid>0000-0002-4755-2668 ; 0000-0003-3338-4154</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Uhttp://www.wanfangdata.com.cn/images/PeriodicalImages/zghxkb/zghxkb.jpg</thumbnail><linktohtml>$$Uhttps://dx.doi.org/10.1016/j.cclet.2019.06.019$$EHTML$$P50$$Gelsevier$$H</linktohtml><link.rule.ids>314,776,780,3536,27903,27904,45974</link.rule.ids></links><search><creatorcontrib>Dai, Qiuzi</creatorcontrib><creatorcontrib>Chen, Jiwei</creatorcontrib><creatorcontrib>Gao, Chunmei</creatorcontrib><creatorcontrib>Sun, Qinsheng</creatorcontrib><creatorcontrib>Yuan, Zigao</creatorcontrib><creatorcontrib>Jiang, Yuyang</creatorcontrib><title>Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents</title><title>Chinese chemical letters</title><description>Herein we discovered a new series of phthalazinone acridine derivatives as PARP and Topo dual inhibitors, with compound 9a exhibited broad antiproliferative activities and induced remarkable apoptosis and S cell cycle arrest in HCT116 cells.
[Display omitted]
In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.</description><subject>Acridines</subject><subject>Antitumor bioactivity</subject><subject>Multitarget</subject><subject>PARP</subject><subject>Topo</subject><issn>1001-8417</issn><issn>1878-5964</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><recordid>eNp9UcFu1DAUtBBIlC1fwMU3LiTY8cZxDhyqUihSpVZVe7Ze7JfES7BXtjel_RI-F7fLmdOMrJmx5g0hHzirOePy8642ZsFcN4z3NZN1gVfkhKtOVW0vt68LZ4xXasu7t-RdSjvGGqWEPCF_vmJyk_9E06PPc-GJgrd0cGEJkzOwUFxhOUB2wdMwUh9WXOh-zjMs8OR88EjBRGddIRajW4t0xZKSqD0U-83Z7c1L5F3YB-r87AaXQ0x0DJHuQ0afXZFBAQPeYKQwlbd0St6MsCR8_w835P7bxd35ZXV1_f3H-dlVZYRoc4UKhOIGeC-HphGs7UFKZL3FYexs023t2Em17RvVceiUQBS8FaV9KwSzOIoN-XjMfQA_gp_0LhyiLz_qp2n-_XNoWFOOxUr2hoij0sSQUsRR76P7BfFRc6afZ9A7_TKDfp5BM6kLFNeXowtLidVh1Mk4LEWti2iytsH91_8XlYiUug</recordid><startdate>20200201</startdate><enddate>20200201</enddate><creator>Dai, Qiuzi</creator><creator>Chen, Jiwei</creator><creator>Gao, Chunmei</creator><creator>Sun, Qinsheng</creator><creator>Yuan, Zigao</creator><creator>Jiang, Yuyang</creator><general>Elsevier B.V</general><general>Department of Pharmacology and Pharmaceutical Sciences, School of Medicine, Tsinghua University, Beijing 100084, China</general><general>The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China%The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China%The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China</general><general>College of Chemistry and Chemical Engineering, Shenzhen University, Shenzhen 518060, China%The State Key Laboratory of Chemical Oncogenomics, Key Laboratory of Chemical Biology, The Graduate School at Shenzhen, Tsinghua University, Shenzhen 518055, China</general><general>Department of Chemistry, Tsinghua University, Beijing 100084, China</general><scope>AAYXX</scope><scope>CITATION</scope><scope>2B.</scope><scope>4A8</scope><scope>92I</scope><scope>93N</scope><scope>PSX</scope><scope>TCJ</scope><orcidid>https://orcid.org/0000-0002-4755-2668</orcidid><orcidid>https://orcid.org/0000-0003-3338-4154</orcidid></search><sort><creationdate>20200201</creationdate><title>Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents</title><author>Dai, Qiuzi ; Chen, Jiwei ; Gao, Chunmei ; Sun, Qinsheng ; Yuan, Zigao ; Jiang, Yuyang</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c335t-e8a381ca196b223059a66e09debf7d274df768492871a783ee31530285330def3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Acridines</topic><topic>Antitumor bioactivity</topic><topic>Multitarget</topic><topic>PARP</topic><topic>Topo</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Dai, Qiuzi</creatorcontrib><creatorcontrib>Chen, Jiwei</creatorcontrib><creatorcontrib>Gao, Chunmei</creatorcontrib><creatorcontrib>Sun, Qinsheng</creatorcontrib><creatorcontrib>Yuan, Zigao</creatorcontrib><creatorcontrib>Jiang, Yuyang</creatorcontrib><collection>CrossRef</collection><collection>Wanfang Data Journals - Hong Kong</collection><collection>WANFANG Data Centre</collection><collection>Wanfang Data Journals</collection><collection>万方数据期刊 - 香港版</collection><collection>China Online Journals (COJ)</collection><collection>China Online Journals (COJ)</collection><jtitle>Chinese chemical letters</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Dai, Qiuzi</au><au>Chen, Jiwei</au><au>Gao, Chunmei</au><au>Sun, Qinsheng</au><au>Yuan, Zigao</au><au>Jiang, Yuyang</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents</atitle><jtitle>Chinese chemical letters</jtitle><date>2020-02-01</date><risdate>2020</risdate><volume>31</volume><issue>2</issue><spage>404</spage><epage>408</epage><pages>404-408</pages><issn>1001-8417</issn><eissn>1878-5964</eissn><abstract>Herein we discovered a new series of phthalazinone acridine derivatives as PARP and Topo dual inhibitors, with compound 9a exhibited broad antiproliferative activities and induced remarkable apoptosis and S cell cycle arrest in HCT116 cells.
[Display omitted]
In this study, we designed and synthesized a series of phthalazinone acridine derivatives as dual PARP and Topo inhibitors. MTT assays indicated that most of the compounds significantly inhibited multiple cancer cells proliferation. In addition, all the compounds displayed Topo II inhibition activity at 10mol/L, and also possessed good PARP-1 inhibitory activities. Subsequent mechanistic studies showed that compound 9a induced remarkable apoptosis and caused prominent S cell cycle arrest in HCT116 cells. Our study suggested that 9a inhibiting Topo and PARP concurrently can be a potential lead compound for cancer therapy.</abstract><pub>Elsevier B.V</pub><doi>10.1016/j.cclet.2019.06.019</doi><tpages>5</tpages><orcidid>https://orcid.org/0000-0002-4755-2668</orcidid><orcidid>https://orcid.org/0000-0003-3338-4154</orcidid></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 1001-8417 |
| ispartof | Chinese chemical letters, 2020-02, Vol.31 (2), p.404-408 |
| issn | 1001-8417 1878-5964 |
| language | eng |
| recordid | cdi_wanfang_journals_zghxkb202002022 |
| source | Elsevier ScienceDirect Journals; Alma/SFX Local Collection |
| subjects | Acridines Antitumor bioactivity Multitarget PARP Topo |
| title | Design, synthesis and biological evaluation of novel phthalazinone acridine derivatives as dual PARP and Topo inhibitors for potential anticancer agents |
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