Production of alpha,beta-dehidrocurvularina by Penicillium SP. for synthesis and evaluation of derivatives in biological tests

• Grant number: 16/01568-9
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: May 01, 2016
• End date: April 30, 2017
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Roberto Gomes de Souza Berlinck
• Grantee: Daniela Tomazela
• Host Institution: Instituto de Química de São Carlos (IQSC). Universidade de São Paulo (USP). São Carlos , SP, Brazil

Abstract

Secondary metabolites present privileged structures related to their structural architecture and bioactivities. This project aims to use alpha,beta-dehidrocurvularin as molecular scaffold for the preparation of derivatives and analogs to evaluate the biological activities of the products obtained. The enone group of alpha,beta-dehidrocurvularin will be used for the application of a series of reactions aimed at obtaining these derivatives and analogs. The project's first challenge will be to obtain alpha,beta-dehidrocurvularin (3) in good yield, produced by fermentation of Penicillium sp., free from interferents and without the formation of artifacts. The second challenge will be the preparation of alpha,beta-dehidrocurvularin derivatives, using simple reactions, aiming to obtain products in good yields. These will be purified by HPLC, completely identified and will have their biological activity assessed in anti-parasitic (anti-Leishmania sp., and anti-Trypanosoma cruzi), anti-bacterial and anti-fungal, cytotoxic in tumor cell lines and as proteasome inhibitors bioassays. The objective is to obtain derivatives which might be considered as future models to be exploited as bioactive hits.