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Study of analogues based on marine natural products from species ofgenus Laurencia (Rhodophyta, Ceramiales) for the control of neglected tropical diseases

Grant number: 17/07346-0
Support type:Scholarships in Brazil - Post-Doctorate
Effective date (Start): June 01, 2017
Effective date (End): December 31, 2020
Field of knowledge:Biological Sciences - Botany - Applied Botany
Cooperation agreement: Coordination of Improvement of Higher Education Personnel (CAPES)
Principal Investigator:Pio Colepicolo Neto
Grantee:Erika Mattos Stein
Home Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated research grant:16/06931-4 - Biodiversity of marine algae and metabolites of economical impact, AP.BTA.TEM

Abstract

The nature and diversity of chemical structures with pharmacological activity that have been found in marine organisms justifies the search for new compounds that may have applications in various areas of interest. Species of red seaweeds, especially Laurencia spp., are special because of the unprecedented variety of terpenes, acetogenins and other chemical classes they produce that are considered potentially useful for the production of new drugs. In previous investigations with Brazilian Laurencia species, among others non-cytotoxic dihydroceramides isolated and characterized, one, first reported as a natural product, showed activity against Schistosoma mansoni (50 ¼g/mL, 100% mortality in 48h). Reports of the low efficacy of the drug currently available on the market against schistosomiasis and the growing concern about the emergence of resistant strains of parasites associated with the lack of significant advances in the development of new drugs in the last 30 years is a matter of concern. Therefore, faced with a potential molecule to combat the parasite that causes one of the most important neglected tropical diseases in Brazil and in the world, we want to advance the studies in the scope of the improvement of this activity through the molecular modeling and QSAR formalisms for the planning of new active compounds. Thus, with planned synthetic reactions, new structures based on the naturally-obtained molecule is designed to potentiate the previously acquired effect. In addition to the schistosomicidal, molluscicidal and toxicity assays, it is desired to perform metabolomic assays to evaluate the interference of the new compounds in protozoan metabolism, compared to the commercial drug. As well as mass spectrometry imaging assays using MALDI (MALDI-IMS) to assess molecular targets to suggest how the compounds are making morphological changes on males and females tissue, and then suggest potential sites of action of the compounds. (AU)