Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors
A series of novel N9-heterobivalent β-carbolines has been synthesized. All the novel compounds were tested for their anticancer activity against six tumour cell lines in vitro. Among these molecules, compounds 5b, and 5w exhibited strong cytotoxic activities with IC50 value of lower than 20 μM. Acut...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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Taylor & Francis Group
2019-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2018.1497619 |
| _version_ | 1811233127669956608 |
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| author | Liang Guo Qin Ma Wei Chen Wenxi Fan Jie Zhang Bin Dai |
| author_facet | Liang Guo Qin Ma Wei Chen Wenxi Fan Jie Zhang Bin Dai |
| author_sort | Liang Guo |
| collection | DOAJ |
| description | A series of novel N9-heterobivalent β-carbolines has been synthesized. All the novel compounds were tested for their anticancer activity against six tumour cell lines in vitro. Among these molecules, compounds 5b, and 5w exhibited strong cytotoxic activities with IC50 value of lower than 20 μM. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 5b and 5w exhibited that tumour inhibition rate of over 40% in the Sarcoma 180 and Lewis lung cancer animal models. Preliminary structure–activity relationships (SARs) analysis indicated that: (1) C1-methylation and C7-methoxylation were favorable for increased activities; (2) 3-Pyridyl or 2-thienyl group substituent into position-1 of the β-carboline core, and the aryl substituent into another β-carboline ring might be detrimental to cytotoxic effects of this class compounds. Investigation of the preliminary mechanism of action demonstrated that compound 5b had obvious angiogenesis inhibitory effects in the chicken chorioallantoic membrane (CAM) assay. |
| first_indexed | 2024-04-12T11:16:17Z |
| format | Article |
| id | doaj.art-f2cdb5f2389a4b1f95de530f08ac22ee |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-04-12T11:16:17Z |
| publishDate | 2019-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-f2cdb5f2389a4b1f95de530f08ac22ee2022-12-22T03:35:30ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742019-01-0134137538710.1080/14756366.2018.14976191497619Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitorsLiang Guo0Qin Ma1Wei Chen2Wenxi Fan3Jie Zhang4Bin Dai5Shihezi UniversityXinJiang Huashidan Pharmaceutical Research Co. Ltd.XinJiang Huashidan Pharmaceutical Research Co. Ltd.XinJiang Huashidan Pharmaceutical Research Co. Ltd.Shihezi UniversityShihezi UniversityA series of novel N9-heterobivalent β-carbolines has been synthesized. All the novel compounds were tested for their anticancer activity against six tumour cell lines in vitro. Among these molecules, compounds 5b, and 5w exhibited strong cytotoxic activities with IC50 value of lower than 20 μM. Acute toxicities and antitumor efficacies of the selected compounds in mice were also evaluated, compounds 5b and 5w exhibited that tumour inhibition rate of over 40% in the Sarcoma 180 and Lewis lung cancer animal models. Preliminary structure–activity relationships (SARs) analysis indicated that: (1) C1-methylation and C7-methoxylation were favorable for increased activities; (2) 3-Pyridyl or 2-thienyl group substituent into position-1 of the β-carboline core, and the aryl substituent into another β-carboline ring might be detrimental to cytotoxic effects of this class compounds. Investigation of the preliminary mechanism of action demonstrated that compound 5b had obvious angiogenesis inhibitory effects in the chicken chorioallantoic membrane (CAM) assay.http://dx.doi.org/10.1080/14756366.2018.1497619heterobivalent β-carbolinecytotoxic activitiesangiogenesis inhibitorsstructure–activity relationship |
| spellingShingle | Liang Guo Qin Ma Wei Chen Wenxi Fan Jie Zhang Bin Dai Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors Journal of Enzyme Inhibition and Medicinal Chemistry heterobivalent β-carboline cytotoxic activities angiogenesis inhibitors structure–activity relationship |
| title | Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors |
| title_full | Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors |
| title_fullStr | Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors |
| title_full_unstemmed | Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors |
| title_short | Synthesis and biological evaluation of novel N9-heterobivalent β-carbolines as angiogenesis inhibitors |
| title_sort | synthesis and biological evaluation of novel n9 heterobivalent β carbolines as angiogenesis inhibitors |
| topic | heterobivalent β-carboline cytotoxic activities angiogenesis inhibitors structure–activity relationship |
| url | http://dx.doi.org/10.1080/14756366.2018.1497619 |
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