Strategies towards potent trypanocidal drugs: Application of Rh-catalyzed [2 + 2 + 2] cycloadditions, sulfonyl phthalide annulation and nitroalkene reactions for the synthesis of substituted quinones and their evaluation against Trypanosoma cruzi

University of Bristol. School of Chemistry. Bristol, UK.
Indian Institute of Technology Bombay. Department of Chemistry. Mumbai, India.
Universidade Federal de Minas Gerais. Insituto de Ciências Extas. Departamento de Química. Belo Horizonte, MG, Brasil.
Universidade Federal de Mato Grosso do Sul. Insituto de Química. Campo Grande, MS, Brasil.
Universidade Federal de Mato Grosso do Sul. Insituto de Química. Campo Grande, MS, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia. Rio de Janeiro, RJ, Brasil.
Fundação Oswaldo Cruz. Instituto Oswaldo Cruz. Laboratório de Biologia. Rio de Janeiro, RJ, Brasil.
Indian Institute of Technology Bombay. Department of Chemistry. Mumbai, India.
University of Bristol. School of Chemistry. Bristol, UK / University of Liverpool, Department Chemistry. Liverpool, United Kingdom.
Universidade Federal de Minas Gerais. Insituto de Ciências Extas. Departamento de Química. Belo Horizonte, MG, Brasil.

Abstract

Rhodium-catalyzed [2 + 2 + 2] cycloadditions, sulfonyl phthalide annulations and nitroalkene reactions have been employed for the synthesis of 56 quinone-based compounds. These were evaluated against Trypanosoma cruzi, the parasite that causes Chagas disease. The reactions described here are part of a program that aims to utilize modern, versatile and efficient synthetic methods for the one or two step preparation of trypanocidal compounds. We have identified 9 compounds with potent activity against the parasite; 3 of these were 30-fold more potent than benznidazole (Bz), a drug used for the treatment of Chagas disease. This article provides a comprehensive outline of reactions involving over 120 compounds aimed at the discovery of new quinone-based frameworks with activity against T. cruzi.

Keywords in Portuguese

Doença de Chagas
Quinones
Anulação
Nitroalquenos
Cicloadições [2 + 2 + 2] catalisadas por Rh

Keywords

Quinones
Chagas disease
Rh-catalyzed [2 + 2 + 2] cycloadditions
Annulation
Nitroalkenes

Publisher

Elsevier

Citation

WOOD, James M. et al. Strategies towards potent trypanocidal drugs: Application of Rh-catalyzed [2 + 2 + 2] cycloadditions, sulfonyl phthalide annulation and nitroalkene reactions for the synthesis of substituted quinones and their evaluation against Trypanosoma cruzi. Biorganic & Medicinal Chemistry, v. 28, 115565, 11p, May 2020.

DOI

10.1016/j.bmc.2020.115565

ISSN

0968-0896

Please use this identifier to cite or link to this item: https://www.arca.fiocruz.br/handle/icict/43092

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