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...
| Main Authors: | , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2021-02-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/22/4/1711 |
| Summary: | 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. |
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| ISSN: | 1661-6596 1422-0067 |