Characterization, purification and studies of chemical and enzymatic stability of synthetic intermediates and targeted dendrimer potentially active in Chagas Disease

• Grant number: 16/11555-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Effective date (Start): September 01, 2016
• Effective date (End): August 31, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Jeanine Giarolla Vargas
• Grantee: Jennifer Midori Shikay
• Host Institution: Faculdade de Ciências Farmacêuticas (FCF). Universidade de São Paulo (USP). São Paulo , SP, Brazil

Abstract

Neglected diseases, such as Chagas disease, are a major public health concern in many countries and regions. The drugs available in therapy are generally toxic and show questionable efficacy. Therefore, the discovery and design of new chemotherapeutic drugs are sorely needed. On the other hand, dendrimers are new molecular architectures with nanoscopic structures, extremely organized with defined molecular weight. They have several advantages over traditional polymers and may act as carriers of drugs, enabling them to controlled release. Considering that, we have proposed to obtain targeted dendrimer for Chagas disease, which is Postdoctoral proposal of this Suppervisor, to be held at the Institute of Chemistry, University of São Paulo, under the supervision of Prof. Dra. M. Têresa Machini, specialist in peptide synthesis. The prodrug will be designed with succinic acid as the core, branching containing lysine and arginine, and 3-hidroxiflavona as active compound. The dipeptide can be cleaved by cruzain, interesting target in the planning of new antichagasic. The objectives of the Undergraduate student's project will be assist some steps of the purification and characterization of the obtained intermediates and final product, as well as perform studies concerning chemical and enzymatic stability, in order to evaluate the release profile of the active substance.

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, 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. (16/11555-1, 15/19438-1)