Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway
A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly,...
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MDPI AG
2018-08-01
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| Series: | Molecules |
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| Online Access: | http://www.mdpi.com/1420-3049/23/8/1972 |
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| author | Yu-Ying Zhang Qian-Qian Zhang Jia-Li Song Liang Zhang Cheng-Shi Jiang Hua Zhang |
| author_facet | Yu-Ying Zhang Qian-Qian Zhang Jia-Li Song Liang Zhang Cheng-Shi Jiang Hua Zhang |
| author_sort | Yu-Ying Zhang |
| collection | DOAJ |
| description | A series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 μM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted. |
| first_indexed | 2024-12-12T10:45:06Z |
| format | Article |
| id | doaj.art-d0aa5cf011df45e886c0e95dc3e35f04 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-12-12T10:45:06Z |
| publishDate | 2018-08-01 |
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| series | Molecules |
| spelling | doaj.art-d0aa5cf011df45e886c0e95dc3e35f042022-12-22T00:26:56ZengMDPI AGMolecules1420-30492018-08-01238197210.3390/molecules23081972molecules23081972Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent PathwayYu-Ying Zhang0Qian-Qian Zhang1Jia-Li Song2Liang Zhang3Cheng-Shi Jiang4Hua Zhang5School of Biological Science and Technology, University of Jinan, Jinan 250022, ChinaSchool of Biological Science and Technology, University of Jinan, Jinan 250022, ChinaSchool of Biological Science and Technology, University of Jinan, Jinan 250022, ChinaThe Key Laboratory of Animal Resistant Biology of Shandong College of Life Sciences, Shandong Normal University, Jinan 250014, ChinaSchool of Biological Science and Technology, University of Jinan, Jinan 250022, ChinaSchool of Biological Science and Technology, University of Jinan, Jinan 250022, ChinaA series of novel coumarin/2-cyanoacryloyl hybrids were prepared and evaluated for their in vitro anticancer activity. Among them, two analogs 5p and 5q showed promising antiproliferative activity against a panel of cancer cell lines, including A549, H157, HepG2, MCF7, MG63, and U2OS. Particularly, 5q showed the most potent activity towards MG63 cells with an IC50 value of 5.06 ± 0.25 μM. Morphological observation and 4,6-diamidino-2-phenylindole (DAPI) staining assay showed that 5q-treated MG63 cells displayed significant apoptosis characteristics. Moreover, flow cytometric detection of phosphatidylserine externalization revealed that 5q induced MG63 apoptosis in a dose-dependent manner. Real-time PCR and western blot assay further confirmed that 5q had strong effects to induce MG63 cell apoptosis, suggesting that the action was associated with down-regulation of the anti-apoptotic protein Bcl-2, upregulation of pro-apoptotic protein Bax, and induced activation of caspase-3, 8, and 9. The present results provide a new chemotype for anticancer drug development and continuing investigation into candidates with coumarin/2-cyanoacryloyl scaffold is warranted.http://www.mdpi.com/1420-3049/23/8/1972coumarin2-cyanoacryloylantiproliferative activityapoptosiscaspase |
| spellingShingle | Yu-Ying Zhang Qian-Qian Zhang Jia-Li Song Liang Zhang Cheng-Shi Jiang Hua Zhang Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway Molecules coumarin 2-cyanoacryloyl antiproliferative activity apoptosis caspase |
| title | Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway |
| title_full | Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway |
| title_fullStr | Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway |
| title_full_unstemmed | Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway |
| title_short | Design, Synthesis, and Antiproliferative Evaluation of Novel Coumarin/2-Cyanoacryloyl Hybrids as Apoptosis Inducing Agents by Activation of Caspase-Dependent Pathway |
| title_sort | design synthesis and antiproliferative evaluation of novel coumarin 2 cyanoacryloyl hybrids as apoptosis inducing agents by activation of caspase dependent pathway |
| topic | coumarin 2-cyanoacryloyl antiproliferative activity apoptosis caspase |
| url | http://www.mdpi.com/1420-3049/23/8/1972 |
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