{"title":"具有苄氧基取代基的联苯氨基喹啉衍生物的合成与 SAR 研究,有望成为抗癌药物","authors":"Yu-Chieh Wu, Meng-Tien Lu, Sheng-Chu Kuo, Po-Chen Chu, Chih-Shiang Chang","doi":"10.1111/cbdd.14509","DOIUrl":null,"url":null,"abstract":"<p>The biphenyl scaffold represents a prominent privileged structure within the realms of organic chemistry and drug development. Biphenyl derivatives have demonstrated notable biological activities, including antimicrobial, anti-inflammatory, anti-HIV, and the treatment of neuropathic pain. Importantly, their anticancer abilities should not be underestimated. In this context, the present study involves the design and synthesis of a series of biphenyl derivatives featuring an additional privileged structure, namely the quinoline core. We have also diversified the substituents attached to the benzyloxy group at either the <i>meta</i> or <i>para</i> position of the biphenyl ring categorized into two distinct groups: [4,3′]biphenylaminoquinoline-substituted and [3,3′]biphenylaminoquinoline-substituted compounds. We embarked on an assessment of the cytotoxic activities of these derivatives in colorectal cancer cell line SW480 and prostate cancer cell line DU145 for exploring the structure–activity relationship. Furthermore, we determined the IC<sub>50</sub> values of selected compounds that exhibited superior inhibitory effects on cell viability against SW480, DU145 cells, as well as MDA-MB-231 and MiaPaCa-2 cells. Notably, [3,3′]biphenylaminoquinoline derivative <b>7j</b> displayed the most potent cytotoxicity against these four cancer cell lines, SW480, DU145, MDA-MB-231, and MiaPaCa-2, with IC<sub>50</sub> values of 1.05 μM, 0.98 μM, 0.38 μM, and 0.17 μM, respectively. This highly promising outcome underscores the potential of [3,3′]biphenylaminoquinoline <b>7j</b> for further investigation as a prospective anticancer agent in future research endeavors.</p>","PeriodicalId":143,"journal":{"name":"Chemical Biology & Drug Design","volume":null,"pages":null},"PeriodicalIF":3.2000,"publicationDate":"2024-04-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis and SAR investigation of biphenylaminoquinoline derivatives with benzyloxy substituents as promising anticancer agents\",\"authors\":\"Yu-Chieh Wu, Meng-Tien Lu, Sheng-Chu Kuo, Po-Chen Chu, Chih-Shiang Chang\",\"doi\":\"10.1111/cbdd.14509\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>The biphenyl scaffold represents a prominent privileged structure within the realms of organic chemistry and drug development. Biphenyl derivatives have demonstrated notable biological activities, including antimicrobial, anti-inflammatory, anti-HIV, and the treatment of neuropathic pain. Importantly, their anticancer abilities should not be underestimated. In this context, the present study involves the design and synthesis of a series of biphenyl derivatives featuring an additional privileged structure, namely the quinoline core. We have also diversified the substituents attached to the benzyloxy group at either the <i>meta</i> or <i>para</i> position of the biphenyl ring categorized into two distinct groups: [4,3′]biphenylaminoquinoline-substituted and [3,3′]biphenylaminoquinoline-substituted compounds. We embarked on an assessment of the cytotoxic activities of these derivatives in colorectal cancer cell line SW480 and prostate cancer cell line DU145 for exploring the structure–activity relationship. Furthermore, we determined the IC<sub>50</sub> values of selected compounds that exhibited superior inhibitory effects on cell viability against SW480, DU145 cells, as well as MDA-MB-231 and MiaPaCa-2 cells. Notably, [3,3′]biphenylaminoquinoline derivative <b>7j</b> displayed the most potent cytotoxicity against these four cancer cell lines, SW480, DU145, MDA-MB-231, and MiaPaCa-2, with IC<sub>50</sub> values of 1.05 μM, 0.98 μM, 0.38 μM, and 0.17 μM, respectively. This highly promising outcome underscores the potential of [3,3′]biphenylaminoquinoline <b>7j</b> for further investigation as a prospective anticancer agent in future research endeavors.</p>\",\"PeriodicalId\":143,\"journal\":{\"name\":\"Chemical Biology & Drug Design\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":3.2000,\"publicationDate\":\"2024-04-29\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Chemical Biology & Drug Design\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.14509\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Chemical Biology & Drug Design","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1111/cbdd.14509","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
Synthesis and SAR investigation of biphenylaminoquinoline derivatives with benzyloxy substituents as promising anticancer agents
The biphenyl scaffold represents a prominent privileged structure within the realms of organic chemistry and drug development. Biphenyl derivatives have demonstrated notable biological activities, including antimicrobial, anti-inflammatory, anti-HIV, and the treatment of neuropathic pain. Importantly, their anticancer abilities should not be underestimated. In this context, the present study involves the design and synthesis of a series of biphenyl derivatives featuring an additional privileged structure, namely the quinoline core. We have also diversified the substituents attached to the benzyloxy group at either the meta or para position of the biphenyl ring categorized into two distinct groups: [4,3′]biphenylaminoquinoline-substituted and [3,3′]biphenylaminoquinoline-substituted compounds. We embarked on an assessment of the cytotoxic activities of these derivatives in colorectal cancer cell line SW480 and prostate cancer cell line DU145 for exploring the structure–activity relationship. Furthermore, we determined the IC50 values of selected compounds that exhibited superior inhibitory effects on cell viability against SW480, DU145 cells, as well as MDA-MB-231 and MiaPaCa-2 cells. Notably, [3,3′]biphenylaminoquinoline derivative 7j displayed the most potent cytotoxicity against these four cancer cell lines, SW480, DU145, MDA-MB-231, and MiaPaCa-2, with IC50 values of 1.05 μM, 0.98 μM, 0.38 μM, and 0.17 μM, respectively. This highly promising outcome underscores the potential of [3,3′]biphenylaminoquinoline 7j for further investigation as a prospective anticancer agent in future research endeavors.
期刊介绍:
Chemical Biology & Drug Design is a peer-reviewed scientific journal that is dedicated to the advancement of innovative science, technology and medicine with a focus on the multidisciplinary fields of chemical biology and drug design. It is the aim of Chemical Biology & Drug Design to capture significant research and drug discovery that highlights new concepts, insight and new findings within the scope of chemical biology and drug design.