Design and synthesis of VEGFR-2 inhibitors based on oleanolic acid moiety

Abstract

In this study, twenty-four oleanolic acid (OA) derivatives were rationally designed based on molecule docking studies and their VEGFR-2 inhibitory activities were tested by Homogeneous time-resolved fluorescence (HTRF) method in vitro. All of the synthesized compounds were identified as new compounds, and the structures of these compounds were determined by ¹H-NMR and ESI-MS. In the screening for VEGFR-2 inhibitors, compounds I₆ and I₇ exhibited excellent inhibitory effect. The results indicated that insertion of phenylurea group with a linker at position C-28 of OA can increase the activity against VEGFR-2 significantly.

Graphical Abstract

Keywords:

• Oleanolic acid derivative
• VEGFR-2 inhibitor
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by the National Natural Science Foundation of China (No. 21372156), the Natural Science Foundation of Liaoning Province (No. 2015020687), innovation team of colleges of Liaoning Provincial Department of Education (Grant No. LT2017009), the Science Foundation of Liaoning Province Department of Education (No. LFD2017004), and key R & D project of Liaoning Province (No. 2019JH2/10300034).