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Potential antichagasics and leishmanicides: synthesis of dendrimer prodrugs of 3-hydroxyflavone

Grant number: 12/19031-0
Support Opportunities:Scholarships in Brazil - Doctorate
Effective date (Start): October 01, 2013
Effective date (End): September 30, 2016
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Elizabeth Igne Ferreira
Grantee:Soraya da Silva Santos
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil


Chagas' disease and leishmaniasis are neglected tropical diseases that affect primarily areas of extreme poverty and are caused by protozoa Trypanosoma cruzi and Leishmania sp., respectively. The chemotherapeutic agents available for these two diseases are scarce and of limited effectiveness, toxics and rouse resistance.Considering that the discovery and the development of new antichagasic and leishmanicide agents are urgently needed, the importance of prodrug design to the improvement of drugs and bioactive compounds and the versatility of dendrimers as drug carriers using different cores and branches the objective of this work is the synthesis of different first generation dendrimer prodrug of 3-hydroxyflavone, that shows potential antichagasic and leishmanicide activity. Thus, we intend to obtain controlled release, improvement of the permeability, reduction of the toxicity and increase of efficacy of this bioactive agent. In this study eight dendrimer prodrugs of 3-hydroxyflavone are proposed, the dendrimers will have propanediamine, butanediamine, hexanediamine or 2,4,6-triamino-1,3,5-triazine as core groups and dendrons built with L-malic acid or L-glutamic acid as spacer groups. In addition, we will evaluate the influence of these cores and spacers in the behavior of the prodrugs with respect to the release, permeability and cytotoxicity. Molecular modeling methods will be applied to predict the bioactive compound releasing from the first generation dendrimer prodrugs of 3-hydroxyflavone. (AU)

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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)
SANTOS, SORAYA DA SILVA; FERREIRA, ELIZABETH IGNE; GIAROLLA, JEANINE. Dendrimer Prodrugs. Molecules, v. 21, n. 6, . (12/19031-0, 15/19438-1)
Academic Publications
(References retrieved automatically from State of São Paulo Research Institutions)
SANTOS, Soraya da Silva. Potential antichagasic and leishmanicide compounds: study of synthesis conditions of 3-hydroxyflavone dendrimer prodrugs. 2016. Doctoral Thesis - Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ) São Paulo.

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