The Synthesis, Structural Modification and Mode of Anticancer Action of Evodiamine: A Review

Background: Finding novel antitumor reagents from naturally occurring alkaloids is a widely accepted strategy. Evodiamine, a tryptamine indole alkaloid isolated from Evodia rutaecarpa, has a wide range of biological activities, such as anti-tumor, anti-inflammation, and anti-bacteria. Hence, research on the structural modification of evodiamine will facilitate the discovery of new antitumor drugs. Objective: The recent advances in the synthesis of evodiamine, and studies on the drug design, biological activities, and structure-activity-relationships of its derivatives, published in patents and primary literature, are reviewed in this paper. Methods: The literature, including patents and follow-up research papers from 2015 to 2020, related to evodiamine is searched in the Scifinder, PubMed, Espacenet, China National Knowledge Infrastructure (CNKI), and Wanfang databases. The keywords are evodiamine, synthesis, modification, anticancer, mechanism. Results: The synthesis of evodiamine is summarized. Then, structural modifications of evodiamine are described, and the possible modes of action are discussed. Conclusion: Evodiamine has a 6/5/6/6/6 ring system, and the structural modifications are focused on rings A, D, E, C5, N-13, and N-14. Some compounds show promising anticancer potentials and warrant further study.