Synthesis of novel anthracycline derivatives containing azido glycosides

• Grant number: 15/10837-0
• Support Opportunities: Scholarships in Brazil - Doctorate
• Start date: September 01, 2015
• End date: May 11, 2018
• Field of knowledge: Health Sciences - Pharmacy
• Principal Investigator: Ivone Carvalho
• Grantee: Maristela Braga Martins Teixeira
• Host Institution: Faculdade de Ciências Farmacêuticas de Ribeirão Preto (FCFRP). Universidade de São Paulo (USP). Ribeirão Preto , SP, Brazil
• Associated scholarship(s): 16/21194-6 - Synthesis of 2-deoxyglycoside derivatives of anthracyclines, BE.EP.DR

Abstract

Doxorubicin is an antineoplastic drug belonging to the anthracyclines class, which lies amongst the most effective chemotherapeutics in clinical use for cancer treatment. They are constituted by a quinone/hydroquinone-type ring system and a glycosidic unit called daunosamine, and act as DNA-intercalating agents, oxidative stress inductors and topoisomerase II poisons, the main mechanisms behind their anticancer activity. Despite their broad efficacy, two major limitations are associated to doxorubicin: multidrug resistance and cardiotoxicity. Anthracycline derivatives containing different glycones and azido groups have showed promising activity, such as reduced cardiac toxicity and multidrug resistance supression in tumoral cell lines. The aim of this project is the semi-synthetic preparation of novel doxorubicin derivatives containing azido glycosides, not exploited in combination with anthracyclines yet, in the search for compounds with greater efficacy and lower toxicity. For this purpose, by means of appropriate orthogonal protections, chemical modifications will be performed directly from doxorubicin, including the cleavage of the glycosyl bond, followed by glycosylation reactions with selected glycosyl donors containing azido groups. Subsequent reactions with the derivatives so obtained could broaden their chemical and structural diversity. Synthesized compounds will be assessed towards cytotoxic activity on tumoral cell lines and on cardiomyocytes cultures, as an indication of their antineoplastic efficacy and cardiotoxicity.

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)

MARTINS-TEIXEIRA, MARISTELA B.; CARVALHO, IVONE. Antitumour Anthracyclines: Progress and Perspectives. CHEMMEDCHEM, v. 15, n. 11, MAY 2020. (15/10837-0)

Academic Publications

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

TEIXEIRA, Maristela Braga Martins. Synthesis of novel anthracycline derivatives containing azido glycosides. 2018. Doctoral Thesis - Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas de Ribeirão Preto (PCARP/BC) Ribeirão Preto.