Synthesis and studies of bioactive compounds release from dendrimer prodrugs and targeted drugs potentially active in neglected diseases

• Grant number: 15/19438-1
• Support type: Regular Research Grants
• Duration: February 01, 2016 - January 31, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Jeanine Giarolla Vargas
• Grantee: Jeanine Giarolla Vargas
• Home Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Assoc. researchers: Elizabeth Igne Ferreira

Abstract

Neglected diseases are a major public health concern in many countries and regions. The drugs available in therapy generally are toxic and showed questionable efficacy. Therefore, the discovery and design of new chemotherapeutic compounds are sorely needed. In this context, the dendrimeric prodrugs may be useful. However, the active compound must be released from dendrimer and the prediction of cleavage behavior represents significant challenge for the scientific community. Considering that, the objective of this project is to synthesize peptide target dendrimer for Chagas' disease, containing succinic acid as the core and branches with lysine, arginine and active compound. The dipeptide may be cleaved by cruzain, promising target in the planning of new antichagasic. These reactions will be performed in solid phase, method widely used in peptides synthesis. The aim also includes, in collaboration with the Laboratory of Design and Synthesis of Chemotherapeutics Potentially Active in Neglected Diseases - LAPEN - Faculty of Pharmaceutical Sciences, University of São Paulo, whose coordinator is Professor Elizabeth Igne Ferreira, the creation of new sector related to the stabilities assays of dendrimeric compounds potentially active in neglected diseases. The pharmacokinetic profile is extremely relevant in the design of new drugs, especially when it considered labile compounds, prodrugs or targeted drugs, originated from prodrug design, which depend on the release to achieve blood levels and/or appropriate cell. Thus, studies of chemical and enzymatic stability of dendrimeric prodrugs assist the comprehension of the molecule behavior in the human body, especially when complex architectures is considered, such as the dendrimers proposed here. In parallel, it will be performed molecular modeling studies, especially molecular dynamics simulations with carboxylesterase, which may support in understanding the mechanisms of hydrolysis of these derivatives. (AU)

Scientific publications

(4)

(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)

GONZAGA, RODRIGO VIEIRA; SANTOS, SORAYA DA SILVA; DA SILVA, JOAO VITOR; PRIETO, DIEGO CAMPOS; SAVINO, DEBORA FELICIANO; GIAROLLA, JEANINE; FERREIRA, ELIZABETH IGNE. Targeting Groups Employed in Selective Dendrons and Dendrimers. PHARMACEUTICS, v. 10, n. 4 DEC 2018. Web of Science Citations: 0.

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 NOV 2018. Web of Science Citations: 6.

SANTOS, S. S.; GONZAGA, R. V.; SILVA, J. V.; SAVINO, D. F.; PRIETO, D.; SHIKAY, J. M.; SILVA, R. S.; PAULO, L. H. A.; FERREIRA, E. I.; GIAROLLA, J. Peptide dendrimers: drug/gene delivery and other approaches. Canadian Journal of Chemistry, v. 95, n. 9, p. 907-916, SEP 2017. Web of Science Citations: 9.

SANTOS, SORAYA DA SILVA; FERREIRA, ELIZABETH IGNE; GIAROLLA, JEANINE. Dendrimer Prodrugs. Molecules, v. 21, n. 6 JUN 2016. Web of Science Citations: 7.