Synthesis and biological evaluation of glycoclusters with potential antiparasitic, antimicrobial and antitumor activities.

• Grant number: 13/27038-8
• Support Opportunities: Scholarships in Brazil - Doctorate
• Effective date (Start): May 01, 2014
• Effective date (End): November 30, 2017
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Ivone Carvalho
• Grantee: Andreza da Silva Figueredo
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil

Abstract

Carbohydrates are polifunctional molecules that play an important role in many physiological and pathological processes when attached covalently to proteins or lipids, in the form of glyconjugates. Recognition growth and differentiation cellular processes, signal transduction, infection by viruses, bacteria and protozoa, and immune response can highlight these events. This large array of activities makes carbohydrates and their glyconjugates interesting biological targets for various pathological conditions, such as cancer, autoimmune diseases, viral, bacterial and parasitic diseases and, consequently, for the development of new diagnostic and therapeutic strategies. This fact has stimulated the synthesis of various glyconjugates, such as glycopolymers and, more recently, glycoclusters and glycodendrimers. The first glycoclusters and glycodendrimers were described in 1993 as synthetic carbohydrate-based biomacromolecules capable to mimic glyconjugates in the biological system. Carbohydrate moieties of these multivalent structures confer high specificity and strong interaction with proteins that recognize carbohydrate (lectins) and enzymes, explaining the therapeutic potential for these diverses, such as enzyme inhibitors and drug carriers. Additionally, the branched structure of these molecules increases the possibilities of exploiting multivalency and polifuncionalização. Thereby, the use of Copper-catalyzed azide-alkyne cycloaddition (CuAAC) has been described in the literature to obtain these molecules. Thus, CuAAC reactions have been used for afford the triazole group wiht physicochemical properties that favor the discovery of new drugs. Based on the interesting therapeutic potential of glycoclusters and glycodendrimers and applicability of CUAAC reactions, the aim of this work is to synthesize and evaluate the potential antiparasitic, antimicrobial and antitumoral activities of glycoclusters in the literature. The glycoclusters will be obtained from CuAAC reactions between pentaerythritol and dipentaerythritol blocks functionalized with propargyl group and carbohydrate functionalized with azido group. According the activity previously described in the literature, the carbohydrates selected for the preparation of glycoclusters were related to (i) galactose, due to the antiparasitic activity, (ii) neamine and azide- cyclitol, due to the antimicrobial activity, and (iii) Tn and TF antigens and N-acetyllactosamine due to the antitumor activity. The biological evaluation of these glycoclusters will comprise cellular cytotoxicity assays, inhibition of the trans-sialidase T. cruzi, in vitro trypanocidal activity, antiviral activity and cytotoxicity in cancer cell lines.

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)

FIGUEREDO, ANDREZA S.; DE ANDRADE, PETERSON; RIUL, THALITA B.; MARCHIORI, MARCELO F.; DE LEO, THAIS CANASSA; FLEURI, ANNA KAROLINE A.; SCHENKMAN, SERGIO; BARUFFI, MARCELO D.; CARVALHO, IVONE. Galactosyl and sialyl clusters: synthesis and evaluation against T. cruzi parasite. Pure and Applied Chemistry, v. 91, n. 7, p. 1191-1207, JUL 2019. (13/27038-8)

FIGUEREDO, ANDREZA S.; ZAMONER, LUIS O. B.; REJZEK, MARTIN; FIELD, ROBERT A.; CARVALHO, IVONE. Cluster glycosides and heteroglycoclusters presented in alternative arrangements. Tetrahedron Letters, v. 59, n. 50, p. 4405-4409, DEC 12 2018. (13/27038-8)

Academic Publications

(References retrieved automatically from State of São Paulo Research Institutions)

FIGUEREDO, Andreza da Silva. Synthesis and biological evaluation of glycoclusters with potential applications in diabetes and Chagas disease. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.