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Modified PAMAM dendrimer with 4-carbomethoxypyrrolidone as a potentially tuberculostatic prodrug

Grant number: 19/03018-4
Support Opportunities:Scholarships abroad - Research Internship - Scientific Initiation
Effective date (Start): July 08, 2019
Effective date (End): September 07, 2019
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Jeanine Giarolla Vargas
Grantee:Renan Vinicius de Araujo
Supervisor: Joern Bolstad Christensen
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Research place: University of Copenhagen, Copenhagen, Denmark  
Associated to the scholarship:17/21154-7 - First generation polyamidoamine (PAMAM): design and synthesis of a potentially active tuberculosis prodrug, BP.IC


Tuberculosis registered, in 2017, 10 million new cases, resulting in 1.4 million of deaths, putting the disease in the top ten death causes in worldwide, and the most fatal infectious disease in the world. In Brazil, there were 72,000 new cases in 2016, with 4,500 deaths, classifying the country as high tuberculosis burden. Dendrimers, on the other hand, have shown a lot of biological application, especially as drug carriers. The dendrimer prodrug, planned by prodrug design, can be useful to improve the pharmacokinetics/pharmaceutical properties of a prototype. There are some downsides to solve regarding dendrimers, considering the inherent toxicity related to peripheral positive charge, as observed in poly(amidoamine) dendrimers (PAMAM). Considering that, the objective of this project is to synthesize PAMAM - G1 derivative prodrug, modified with 4-carboxymethoxypyrrolidone moiety and coupled with succinoylated isoniazid. It is intended, therefore, that when the drug is released, the 4-carboxymethoxypyrrolidone moiety remaining may decrease the dendrimer toxicity. The protection of basic functional groups of PAMAM is widely used by Professor Jørn B. Christensen (University of Copenhagen), collaborator of this project. The prodrug will be structurally characterized and the citotoxicity will be evaluated and compared to unmodified PAMAM. (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)
RENAN VINICIUS DE ARAÚJO; SORAYA SILVA SANTOS; LUCCAS MISSFELDT SANCHES; JEANINE GIAROLLA; OMAR EL SEOUD; ELIZABETH IGNE FERREIRA. Malaria and tuberculosis as diseases of neglected populations: state of the art in chemotherapy and advances in the search for new drugs. Memórias do Instituto Oswaldo Cruz, v. 115, . (17/21154-7, 18/10359-0, 19/03018-4)

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