The Synthesis of Urolithins and their Derivatives and the Modes of Antitumor Action

Abstract

Urolithins are microbial metabolites derived from berries and pomegranate fruits, which display anti-inflammatory, anti-oxidative, and anti-aging activities. There are eight natural urolithins (urolithin A-E, M5, M6 and M7), which have been isolated by now. Structurally, urolithins are phenolic compounds and belong to 6H-dibenzo [b,d] pyran-6-one. They have drawn considerable attention because of their vast range of biological activities and health benefits. Recent studies also suggest that they possess anti-SARS-CoV-2 and anticancer effects. In this article, the recent advances in the synthesis of urolithins and their derivatives from 2015 to 2021 are reviewed. To improve or overcome the solubility and metabolism stability issues, the modifications of urolithins are mainly centered on the hydroxy group and lactone group, and some compounds have been found to display promising results and the potential for further study. The possible modes of antitumor action of urolithin are also discussed. Several signaling pathways, including PI3K-Akt, Wnt/β-catenin pathways, and multiple receptors (aryl hydrocarbon receptor, estrogen and androgen receptors) and enzymes (tyrosinase and lactate dehydrogenase) are involved in the antitumor activity of urolithins.

Keywords: Urolithin; antitumor; derivatives; mode of action; modification; synthesis.