Synthesis and antitumor activity evaluation of ursolic acid derivatives

Abstract

Eighteen uronic acid derivatives were designed and synthesized, and the cytotoxicities in vitro of two cancer cell lines (BEL7402 and SGC7901) were evaluated by MTT assay. The results showed that the inhibitory rate of the compounds on both cell lines was significantly higher than the parent compound. The IC₅₀ of compounds II₄, II₆, III₄, and III₆ are comparable or stronger than the positive control drug, the interactions between compounds II₄, II₆, III₄, III₆, and NF-κB were also studied by docking simulations.

Graphical Abstract

Keywords:

• Ursolic acid derivatives
• synthetic
• anticancer activity
• NF-κB inhibitor

Acknowledgments

We thank Shenyang Pharmaceutical University for the tool and technology assistance in docking studies.

Disclosure statement

No potential conflict of interest was reported by the authors.

Funding

This work was supported by the National Natural Science Foundation of China [21372156]; the Liaoning University Innovation Team Support Project [LT2017009]; the Liaoning Province key R & D project [2019JH2 /10300034]; and the Key projects of Shenyang University of Chemical Technology [LDB2019001].

Figure 1. The structures of compounds 1 and 2.

Figure 2. Binding modes of compound II₄ with NF-κB in 3D and 2D diagram. The H-bond interactions with compounds are shown in green, alkyl-bonds are shown in pink, and sulfur-bonds are shown in yellow.

Figure 3. Binding modes of compound II₆ with NF-κB in 3D and 2D diagram. The H-bond interactions with compounds are shown in green, and alkyl-bonds are shown in pink.

Figure 4. Binding modes of compound III₄ with NF-κB in 3D and 2D diagram. The H-bond interactions with compounds are shown in green, and alkyl-bonds are shown in pink.

Figure 5. Binding modes of compound III₆ with NF-κB in 3D and 2D diagram. The H-bond interactions with compounds are shown in green, and alkyl-bonds are shown in pink.

Correction Statement

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