Design, synthesis and anti-tumor activity of asiatic acid derivatives as VEGF inhibitors

Abstract

The VEGF receptor is mock-coupled with a known active compound and the active groups of the inhibitor which can bind to VEGF were analyzed. Using asiatic acid as a lead compound, 10 novel skeleton candidate compounds were designed through introduction of the active groups onto the special location and synthesized simultaneously. Furthermore, the structure of these compounds was determined by ¹H NMR, ¹³C NMR and MS and 9 compounds were identified as the new compounds. Moreover, the in vitro anti-tumor activities of these new compounds were determined by MTT assay on two cancer cell lines (HepG2 and SGC-7901). The results showed that compounds I₁ and II₂ have more potent anticancer activity than positive control drugs such as gefitinib and paclitaxel.

Graphical Abstract

Keywords:

• Asiatic acid derivatives
• structural modification
• anti-tumor activity
• molecular docking

Disclosure statement

No potential conflict of interest was reported by the authors.

Additional information

Funding

This work was financially supported by National Natural Science Foundation of China [21372156], the Liaoning Province key Research & Development project [2019JH2/10300034], the Shenyang Major Scientific and Technological Achievement Transformation Project [20-203-5-45], the Department of Education Research Project of Liaoning Province [LJ2020025], the Key project of Shenyang University of Chemical Technology [LDB2019001]. Natural Science Research Project of Anhui Province [KJ2021A1340].