Fungal biotransformation of quinonemethide triterpenes and their (new) structure-activity relationship on tumor cell lines

Abstract

Quinonemethide triterpenes (QMTs) are a select group of secondary metabolites that are exclusively biosynthesized by plants of the Celastraceae family. QMTs display a wide range of biological activities, especially antitumor action. Because they can act on several cancer cell lines by multiple mechanisms and reach a multitude of oncogenic targets, they have been labeled "multifunctional drugs". In addition, QMTs are currently considered one of the most promising classes of natural products for drug development. Despite their great importance, preclinical and clinical investigations into QMTs are still difficult because these compounds are poorly soluble. In this context, biotransformation emerges as an attractive biotechnological technique that involves enzymatic reactions carried out by microorganisms that participate mainly in hydroxylation and glycosylation. Moreover, maytenin and maytenol (promising QMTs isolated from Peritassa campestris roots) still need to have their antitumor activity evaluated with a focus on molecular targets. In particular, the antitumor action of maytenol has never been examined. Therefore, this proposed postdoctoral project aims to study maytenin and maytenol biotransformation by fungal strains and to assess the antitumor activity of these compounds and their products by exploring their molecular targets of action, to uncover potent new anticancer QMTs. This project will provide new knowledge about the mechanism of action of QMTs biosynthesized by the Brazilian species P. campestris and of other biotransformed QMTs and will offer critical insights into the potential use of these compounds to treat cancer.