Potential antichagasic and leishmanicide compounds: study of synthesis conditions of 3-hydroxyflavone dendrimer prodrugs

Author(s)

Soraya da Silva Santos

• Document type: Doctoral Thesis
• Press: São Paulo.
• Institution: Universidade de São Paulo (USP). Conjunto das Químicas (IQ e FCF) (CQ/DBDCQ)
• Defense date: 2016-10-24

Examining board members

Elizabeth Igne Ferreira; Reinaldo Camino Bazito; Leoberto Costa Tavares; Carlota de Oliveira Rangel Yagui

• Advisor: Elizabeth Igne Ferreira

Abstract

INTRODUCTION: Chagas\' disease and leishmaniasis are super neglected tropical diseases that affect primarily areas of extreme poverty. The drugs available for these diseases are scarce and of limited effectiveness, toxic and rouse resistance. OBJECTIVE: Considering that 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, the objective of this work was the synthesis of dendrimer prodrug of 3-hydroxyflavone, which shows potential antichagasic and leishmanicide activities. Thus, we intended to obtain controlled release, improvement of the permeability, reduction of the toxicity and increase of efficacy of this bioactive agent. MATERIAL AND METHODS: Convergent and divergent approaches have been used to synthesize those compounds. Synthetic steps consist of protection, deprotection and coupling reactions. RESULTS AND DISCUSSION: The convergent approach presented problems due to the instability of the 3-hydroxyflavone derivatives, in different reaction and purification conditions. However, there is evidence of the synthesis of dendrimer prodrugs, though still impure. Due to instability and purification difficulty of intermediate, we performed the divergent synthesis. We obtained the pure intermediates composed by cores propanediamine and hexanediamine coupled to the protected malic acid as spacer group. CONCLUSION: Synthetic studies suggested the synthesis of dendrimer prodrugs, although impure. The greatest difficulties were the purification and the instability of compounds. (AU)

• FAPESP's process: 12/19031-0 - Potential antichagasics and leishmanicides: synthesis of dendrimer prodrugs of 3-hydroxyflavone
• Grantee: Soraya da Silva Santos
• Support Opportunities: Scholarships in Brazil - Doctorate