| Grant number: | 18/07885-1 |
| Support Opportunities: | BIOTA-FAPESP Program - Regular Research Grants |
| Start date: | August 01, 2018 |
| End date: | July 31, 2020 |
| Field of knowledge: | Physical Sciences and Mathematics - Chemistry - Organic Chemistry |
| Principal Investigator: | João Henrique Ghilardi Lago |
| Grantee: | João Henrique Ghilardi Lago |
| Host Institution: | Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Santo André , SP, Brazil |
| City of the host institution: | Santo André |
| Associated researchers: | André Gustavo Tempone Cardoso ; Joao Luiz Baldim Zanin ; Luiz Felipe Domingues Passero ; Patricia Sartorelli |
| Associated research grant(s): | 19/13906-4 - Discovering new drug leads against Chagas Disease Based on Brazilian bioactive plant molecules, AP.R SPRINT |
Abstract
In the present project will be selected plant species from Sao Paulo State biomes (Atlantic Forest and "Cerrado") aiming the structural characterization of natural products/semisynthetic derivatives with antiparasitic activity as well as evaluation of pre-clinical and toxicological potential, in continuation to the study begun in 2015 with FAPESP funding (project 2015/11936-2). Thus, different species belonging to Lauraceae, Piperaceae and Asteraceae will be collected and their extracts prepared, and those who had proven antiparasitic action (antileishmanial and antitrypanosomal) will be subjected to molecular dereplication procedures (HPLC/MS and NMR) followed to a bioassay-guided fractionation processes. Using this approach, the active metabolites will be purified and their structures will be determined by spectroscopic/spectrometric techniques. After this step, the crude extracts will be standardized by HPLC/DAD and HPLC/MS allowing the identification of the bioactive compound in the vegetable matrix (biomarker). After the recognition of the active substances, they will be submitted to SAR tests through different techniques aiming at the improvement of biological activities by molecular modifications guided by multivariate statistics and prediction models created according to each class of compounds obtained. Additionally, it is intended, in this proposal, to carry out specific tests to define the mode of action of substances with proven antiprotozoal activity in relation to the parasite, especially membrane pore evaluation and ultrastructural studies. Following the standardization biological assays will be carried out. Thus, this project intends to add new compounds and / or extracts with proven herbal pharmacological armamentarium to restricted activity, providing tools for the development of new herbal drugs. (AU)
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