Natural product evodiamine-inspired medicinal chemistry: Anticancer activity, structural optimization and structure-activity relationship

It is a well-known phenomenon that natural products can serve as powerful drug leads to generate new molecular entities with novel therapeutic utility. Evodiamine (Evo), a major alkaloid component in traditional Chinese medicine Evodiae Fructus, is considered a desirable lead scaffold as its multifunctional pharmacological properties. Although natural Evo has suboptimal biological activity, poor pharmacokinetics, low water solubility, and chemical instability, medicinal chemists have succeeded in producing synthetic analogs that overshadow the deficiency of Evo in terms of further clinical application. Recently, several reviews on the synthesis, structural modification, mechanism pharmacological actions, structure-activity relationship (SAR) of Evo have been published, while few reviews that incorporates intensive structural basis and extensive SAR are reported. The purpose of this article is to review the structural basis, anti-cancer activities, and mechanisms of Evo and its derivatives. Emphasis will be placed on the optimizing strategies to improve the anticancer activities, such as structural modifications, pharmacophore combination and drug delivery systems. The current review would benefit further structural modifications of Evo to discover novel anticancer drugs.