Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands
Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and plays a key role in tumor progression. The C-rich DNA sequence of <i>VEGF</i> promoter can form i-motif structure, which is a potential target for the development of novel anticancer agents. However, there is a...
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MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/4/1711 |
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| author | Huang Zeng Shuangshuang Kang Yu Zhang Ke Liu Qian Yu Ding Li Lin-Kun An |
| author_facet | Huang Zeng Shuangshuang Kang Yu Zhang Ke Liu Qian Yu Ding Li Lin-Kun An |
| author_sort | Huang Zeng |
| collection | DOAJ |
| description | Vascular endothelial growth factor (VEGF) is an angiogenic growth factor and plays a key role in tumor progression. The C-rich DNA sequence of <i>VEGF</i> promoter can form i-motif structure, which is a potential target for the development of novel anticancer agents. However, there is a limited number of chemotypes as the selective ligands of <i>VEGF</i> promoter i-motif, which leaves much room for development. Herein, we report the discovery of the natural oleanolic acid scaffold as a novel chemotype for the development of selective ligands of <i>VEGF</i> i-motif. A series of oleanolic acid derivatives as <i>VEGF</i> promoter i-motif ligands were synthesized. Subsequent evaluations showed that <b>3c</b> could selectively bind to and stabilize <i>VEGF</i> promoter i-motif without significant binding to G-quadruplex, duplex DNA, and other oncogene i-motifs. Cell-based assays indicated that <b>3c</b> could effectively downregulate <i>VEGF</i> gene transcription and expression in MCF-7 cells, inhibit tumor cells proliferation and migration, and induce cancer cells apoptosis. This work provides evidence of <i>VEGF</i> promoter i-motif as an anticancer target and will facilitate future efforts for the discovery of oleanolic acid-based selective ligands of <i>VEGF</i> promoter i-motif. |
| first_indexed | 2024-03-09T05:05:28Z |
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| id | doaj.art-d5bbaa1da51e4f688712c5a88b934348 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T05:05:28Z |
| publishDate | 2021-02-01 |
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| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-d5bbaa1da51e4f688712c5a88b9343482023-12-03T12:55:50ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-02-01224171110.3390/ijms22041711Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif LigandsHuang Zeng0Shuangshuang Kang1Yu Zhang2Ke Liu3Qian Yu4Ding Li5Lin-Kun An6School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaSchool of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, ChinaVascular endothelial growth factor (VEGF) is an angiogenic growth factor and plays a key role in tumor progression. The C-rich DNA sequence of <i>VEGF</i> promoter can form i-motif structure, which is a potential target for the development of novel anticancer agents. However, there is a limited number of chemotypes as the selective ligands of <i>VEGF</i> promoter i-motif, which leaves much room for development. Herein, we report the discovery of the natural oleanolic acid scaffold as a novel chemotype for the development of selective ligands of <i>VEGF</i> i-motif. A series of oleanolic acid derivatives as <i>VEGF</i> promoter i-motif ligands were synthesized. Subsequent evaluations showed that <b>3c</b> could selectively bind to and stabilize <i>VEGF</i> promoter i-motif without significant binding to G-quadruplex, duplex DNA, and other oncogene i-motifs. Cell-based assays indicated that <b>3c</b> could effectively downregulate <i>VEGF</i> gene transcription and expression in MCF-7 cells, inhibit tumor cells proliferation and migration, and induce cancer cells apoptosis. This work provides evidence of <i>VEGF</i> promoter i-motif as an anticancer target and will facilitate future efforts for the discovery of oleanolic acid-based selective ligands of <i>VEGF</i> promoter i-motif.https://www.mdpi.com/1422-0067/22/4/1711vascular endothelial growth factoroleanolic acidi-motifgene transcriptional regulationantiproliferationapoptosis |
| spellingShingle | Huang Zeng Shuangshuang Kang Yu Zhang Ke Liu Qian Yu Ding Li Lin-Kun An Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands International Journal of Molecular Sciences vascular endothelial growth factor oleanolic acid i-motif gene transcriptional regulation antiproliferation apoptosis |
| title | Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands |
| title_full | Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands |
| title_fullStr | Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands |
| title_full_unstemmed | Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands |
| title_short | Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands |
| title_sort | synthesis and biological evaluation of oleanolic acid derivatives as selective vascular endothelial growth factor promoter i motif ligands |
| topic | vascular endothelial growth factor oleanolic acid i-motif gene transcriptional regulation antiproliferation apoptosis |
| url | https://www.mdpi.com/1422-0067/22/4/1711 |
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