Cu-catalyzed late-stage diversification and anti-proliferative activity evaluation of evodiamine

TL;DR

Scientists modified a natural compound called evodiamine to create new versions with potential anti-cancer properties.

Contribution

A new method for modifying evodiamine using copper catalysis was developed to improve its anti-tumor activity.

Findings

Direct introduction of aryl groups at the N-13 position of evodiamine led to poor cytotoxicity.

Inserting a pharmacophore fragment between the N-13 position and aryl group improved anti-tumor activity.

The study provides insights for developing more effective evodiamine analogues for cancer treatment.

Abstract

A series of N-13-arylated evodiamine derivatives (3a–3v) were designed and synthesized via a Cu-catalyzed late-stage diversification of the bioactive natural product evodiamine. The antitumor activities of these synthesized derivatives against HCT-116, 4T1, and SU-DHL-6 cells were evaluated in vitro, demonstrating that direct introduction of aryl groups at the N-13 position through C–N coupling led to unsatisfactory cytotoxicity. Based on previous studies, the preliminary structure–activity relationship analysis indicated that inserting a suitable pharmacophore fragment between the N-13 position and the introduced aryl group can enhance the anti-tumor activity of N-13 evodiamine derivatives containing aromatic functional groups. This study provides helpful insights for the further development of antitumor evodiamine analogues.

For N13 evodiamine analogues containing aromatic groups, inserting a suitable pharmacophore fragment between N13 position and introduced aryl group is beneficial for anti-tumor activity.

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