Design, synthesis, and antitumor activity of novel oleanolic acid analogues targeting EGFR

Abstract

Based on the simulated docking of Epidermal growth factor receptor inhibitors with known active small molecule compounds, computer-aided drug design technology was used to analyze key amino acid fragments and determine the active groups binding with key sites. Then, twelve novel analogues of oleanolic acid (OA) were synthesized by introducing active groups at the C-3 and C-28 positions of OA. The structures of these novel analogues were confirmed by NMR and MS. Furthermore, the antitumor activities of these novel analogues were evaluated by MTT assay. As a result, compounds I₃ and II₃ showed stronger cytotoxicity on tumor cells than positive controls. In conclusion, our study synthesized twelve novel analogues of OA and determined compounds I₃ and II₃ had better antitumor effect, which may be potential candidate compounds for tumor therapy.

Keywords:

• Computer-aided drug design
• oleanolic acid
• structural modification
• antitumor activity

Disclosure statement

No potential conflict of interest was reported by the authors.

Correction Statement

This article has been corrected with minor changes. These changes do not impact the academic content of the article.

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 Key Project of Education Department of Liaoning Province [LJKZ0427], the Project of Education Department of Liaoning Province [LJKZ0427], the Shenyang Major Scientific and Technological Achievement Transformation Project [20-203-5-45], the Key Research and Local Service Project of Shenyang University of Chemical Technology [LDB2019001].