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



Wood, JM, Satam, NS, Almeida, RG, Cristani, VS, de Lima, DP, Dantas-Pereira, L, Salomão, K, Menna-Barreto, RFS, Namboothiri, INN, Bower, JF ORCID: 0000-0002-7551-8221
et al (show 1 more authors) (2020) 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. Bioorganic and Medicinal Chemistry, 28 (15).

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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.

Item Type: Article
Uncontrolled Keywords: Quinones, Chagas disease
Depositing User: Symplectic Admin
Date Deposited: 26 Jun 2020 08:10
Last Modified: 08 Feb 2021 15:32
DOI: 10.1016/j.bmc.2020.115565
Related URLs:
URI: https://livrepository.liverpool.ac.uk/id/eprint/3091688