Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents
Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives...
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| Format: | Article |
| Language: | English |
| Published: |
Taylor & Francis Group
2021-01-01
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| Series: | Journal of Enzyme Inhibition and Medicinal Chemistry |
| Subjects: | |
| Online Access: | http://dx.doi.org/10.1080/14756366.2021.1875458 |
| _version_ | 1818332572214624256 |
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| author | Heping Zhu Shilong Ying Bingluo Zhou Xinyang Hu Xiao Liang Wangyu Li Dungai Wang Hongchuan Jin Yuanjiang Pan |
| author_facet | Heping Zhu Shilong Ying Bingluo Zhou Xinyang Hu Xiao Liang Wangyu Li Dungai Wang Hongchuan Jin Yuanjiang Pan |
| author_sort | Heping Zhu |
| collection | DOAJ |
| description | Colorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development. |
| first_indexed | 2024-12-13T13:37:52Z |
| format | Article |
| id | doaj.art-7da09a03c5ed4dd1b7cb29ae53e36650 |
| institution | Directory Open Access Journal |
| issn | 1475-6366 1475-6374 |
| language | English |
| last_indexed | 2024-12-13T13:37:52Z |
| publishDate | 2021-01-01 |
| publisher | Taylor & Francis Group |
| record_format | Article |
| series | Journal of Enzyme Inhibition and Medicinal Chemistry |
| spelling | doaj.art-7da09a03c5ed4dd1b7cb29ae53e366502022-12-21T23:43:42ZengTaylor & Francis GroupJournal of Enzyme Inhibition and Medicinal Chemistry1475-63661475-63742021-01-0136159360410.1080/14756366.2021.18754581875458Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agentsHeping Zhu0Shilong Ying1Bingluo Zhou2Xinyang Hu3Xiao Liang4Wangyu Li5Dungai Wang6Hongchuan Jin7Yuanjiang Pan8Department of Chemistry, Zhejiang UniversityLaboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang UniversityLaboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang UniversityLaboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang UniversityDepartment of Chemistry, Zhejiang UniversityDepartment of Chemistry, Zhejiang UniversityDepartment of Chemistry, Zhejiang UniversityLaboratory of Cancer Biology, Key Lab of Biotherapy in Zhejiang, Sir Run Run Shaw Hospital, Medical School of Zhejiang UniversityDepartment of Chemistry, Zhejiang UniversityColorectal cancer (CRC) is a common malignant tumour of human digestive tract. The high mortality rate of CRC is closely related to the limitations of existing treatments. Thus, there is an urgent need to search for new anti-CRC agents. In this work, twenty novel coumarin-dithiocarbamate derivatives (IDs) were designed, synthesized and evaluated in vitro. The results suggest that the most active compound ID-11 effectively inhibited the proliferation of CRC cell lines while shown little impact on normal colon epithelial cells. Mechanism studies revealed that ID-11 displayed bromodomain-containing protein 4 inhibitory activity, and induced G2/M phase arrest, apoptosis as well as decreased the expression levels of the key genes such as c-Myc and Bcl-2 in CRC cell lines. Moreover, the ADMET properties prediction results shown that ID-11 possess well metabolic characteristics without obvious toxicities. Our data demonstrated that compound ID-11 may be a promising anti-CRC agent and deserved for further development.http://dx.doi.org/10.1080/14756366.2021.1875458colorectal cancercoumarin-dithiocarbamate derivativesbromodomain-containing protein 4antitumor activities |
| spellingShingle | Heping Zhu Shilong Ying Bingluo Zhou Xinyang Hu Xiao Liang Wangyu Li Dungai Wang Hongchuan Jin Yuanjiang Pan Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents Journal of Enzyme Inhibition and Medicinal Chemistry colorectal cancer coumarin-dithiocarbamate derivatives bromodomain-containing protein 4 antitumor activities |
| title | Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents |
| title_full | Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents |
| title_fullStr | Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents |
| title_full_unstemmed | Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents |
| title_short | Design, synthesis, and evaluation of novel coumarin-dithiocarbamate derivatives (IDs) as anti-colorectal cancer agents |
| title_sort | design synthesis and evaluation of novel coumarin dithiocarbamate derivatives ids as anti colorectal cancer agents |
| topic | colorectal cancer coumarin-dithiocarbamate derivatives bromodomain-containing protein 4 antitumor activities |
| url | http://dx.doi.org/10.1080/14756366.2021.1875458 |
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