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First generation polyamidoamine (PAMAM): design and synthesis of a potentially active tuberculosis prodrug

Grant number: 17/21154-7
Support Opportunities:Scholarships in Brazil - Scientific Initiation
Effective date (Start): December 01, 2017
Effective date (End): January 31, 2020
Field of knowledge:Health Sciences - Pharmacy
Principal Investigator:Jeanine Giarolla Vargas
Grantee:Renan Vinicius de Araujo
Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
Associated scholarship(s):19/03018-4 - Modified PAMAM dendrimer with 4-carbomethoxypyrrolidone as a potentially tuberculostatic prodrug, BE.EP.IC


Tuberculosis is part of a group named Neglected Diseases 2.0, which includes "The Big Three" diseases: Malaria, AIDS and Tuberculosis. Combined, they killed around six millions of people worldwide in the last year, according to World Health Organization. For this reason, they have been included in programs such as blue marble health, to encourage research, public policies and investment, as well as in the Global Fund to Fight AIDS, Tuberculosis and Malaria. Considering only tuberculosis, in 2015, 10.4 million of new cases were reported and 1.8 million of deaths were registered, putting it in the top of ten death causes in worldwide. Dendrimers, on the other hand, has 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. Considering that, the objective of this project is to synthesize a dendrimer prodrug containing isoniazid, being, therefore, potentially active in tuberculosis. The latent form will be composed by the first generation of polyamidoamine (PAMAM), succinic acid as spacer and the already mentioned isoniazid, which is one of the drug choice for the treatment of this disease. The main goal is to obtain a controlled drug delivery of the active drug, improving, therefore, the pharmacokinetics profile of the prototype. (AU)

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Scientific publications (5)
(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)
DE ARAUJO, RENAN VINICIUS; SANTOS, SORAYA DA SILVA; FERREIRA, ELIZABETH IGNE; GIAROLLA, JEANINE. New Advances in General Biomedical Applications of PAMAM Dendrimers. Molecules, v. 23, n. 11, . (17/21154-7, 15/19438-1)
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, . (19/03018-4, 17/21154-7, 18/10359-0)
RAMPINI, DENISE; PRIETO, DIEGO CAMPOS; COLZI, ANA LUISA; DE ARAUJO, RENAN VINICIUS; GIAROLLA, JEANINE. Future and Perspectives of the Zika Virus: Drug Repurposing as a Powerful Tool for Treatment Insights. MINI-REVIEWS IN MEDICINAL CHEMISTRY, v. 20, n. 18, p. 1917-1928, . (17/21154-7)
SANTOS, SORAYA SILVA; DE ARAUJO, RENAN VINICIUS; GIAROLLA, JEANINE; EL SEOUD, OMAR; FERREIRA, ELIZABETH IGNE. Searching for drugs for Chagas disease, leishmaniasis and schistosomiasis: a review. INTERNATIONAL JOURNAL OF ANTIMICROBIAL AGENTS, v. 55, n. 4, . (15/19438-1, 17/21154-7)
RAMPINI, DENISE; DE ARAUJO, RENAN VINICIUS; FOITINHO, RODRIGO ESTEVES; LOURENCO, FELIPE REBELLO; GIAROLLA, JEANINE. Analytical Quality by Design as an Important Tool to Determine the Best Analytical Conditions for Isoniazid and Its Respective Succinylated Prodrug. JOURNAL OF AOAC INTERNATIONAL, v. 104, n. 1, p. 239-247, . (17/21154-7)

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