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Synthesis and Biological Evaluation of Oleanolic Acid Derivatives as Selective Vascular Endothelial Growth Factor Promoter i-Motif Ligands
| Content Provider | MDPI |
|---|---|
| Author | Zeng, Huang Kang, Shuangshuang Zhang, Yu Liu, Ke Yu, Qian Li, Ding An, Lin-Kun |
| Copyright Year | 2021 |
| 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 VEGF 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 VEGF 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 VEGF i-motif. A series of oleanolic acid derivatives as VEGF promoter i-motif ligands were synthesized. Subsequent evaluations showed that 3c could selectively bind to and stabilize VEGF promoter i-motif without significant binding to G-quadruplex, duplex DNA, and other oncogene i-motifs. Cell-based assays indicated that 3c could effectively downregulate VEGF gene transcription and expression in MCF-7 cells, inhibit tumor cells proliferation and migration, and induce cancer cells apoptosis. This work provides evidence of VEGF promoter i-motif as an anticancer target and will facilitate future efforts for the discovery of oleanolic acid-based selective ligands of VEGF promoter i-motif. |
| Starting Page | 1711 |
| e-ISSN | 14220067 |
| DOI | 10.3390/ijms22041711 |
| Journal | International Journal of Molecular Sciences |
| Issue Number | 4 |
| Volume Number | 22 |
| Language | English |
| Publisher | MDPI |
| Publisher Date | 2021-02-08 |
| Access Restriction | Open |
| Subject Keyword | International Journal of Molecular Sciences Medicinal Chemistry Vascular Endothelial Growth Factor Oleanolic Acid I-motif Gene Transcriptional Regulation Antiproliferation Apoptosis |
| Content Type | Text |
| Resource Type | Article |
