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

Grant number: 18/00143-0
Support type:Scholarships abroad - Research Internship - Post-doctor
Effective date (Start): March 01, 2018
Effective date (End): February 28, 2019
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal researcher:Maysa Furlan
Grantee:Marielle Cascaes Inácio
Supervisor abroad: Leslie Gunatilaka
Home Institution: Instituto de Química (IQ). Universidade Estadual Paulista (UNESP). Campus de Araraquara. Araraquara , SP, Brazil
Research place: University of Arizona, United States  
Associated to the scholarship:14/19362-2 - Application of biotechnology to evaluate plant-microorganism interaction during production of secondary metabolites in Peritassa campestris and its endophytes, BP.PD


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.

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Scientific publications
(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)
INACIO, MARIELLE CASCAES; PAZ, TIAGO ANTUNES; SOARES PEREIRA, ANA MARIA; FURLAN, MAYSA. Maytenin Plays a Special Role in the Regulation of the Endophytic Bacillus megaterium in Peritassa campestris Adventitious Roots. Journal of Chemical Ecology, v. 45, n. 9, p. 789-797, . (13/07600-3, 14/19362-2, 18/00143-0)

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