Generation and capture of naphthoquinonynes: a new frontier in the development of trypanocidal quinones <i>via</i> aryne chemistry
The regioselective synthesis of functionalized naphthoquinones <i>via</i> the formation and capture of naphthoquinonynes has been used to prepare trypanocidal compounds. The target compounds are functionalized on the aromatic ring, leaving the quinoidal ring intact. Using this technique, eighteen functionalized naphthoquinones were succesfull obtained, divided in two main groups: the first scope using <i>N</i>-nucleophiles, and the second scope using pyridine <i>N</i>-oxides, with yields up to 74%. Evaluation against bloodstream trypomastigotes of <i>T. cruzi</i> has identified fourteen compounds that are more potent than benznidazole (Bz); for instance, compounds 29b-I and 30b, with IC<sub>50</sub>/24 h values of 10.5 and 10.1 μM, respectively, are approximately 10-fold more active than Bz. This study provides the first examples of the application of naphthoquinonyne chemistry for the synthesis of new compounds with potent trypanocidal activities.
Authors
- Laura Figueroa
- Rubem F. S. Menna‐Barreto (ORCID: https://orcid.org/0000-0002-1352-0641)
- Warley de Souza Borges (ORCID: https://orcid.org/0000-0003-4475-1028)
- Maria H. Araújo (ORCID: https://orcid.org/0000-0002-2609-0281)
- Renato L. Carvalho (ORCID: https://orcid.org/0000-0002-8515-9306)
- Emilay B. T. Diogo
- Renata G. Almeida (ORCID: https://orcid.org/0000-0003-2896-0487)
- John F. Bower (ORCID: https://orcid.org/0000-0002-7551-8221)
- James M. Wood (ORCID: https://orcid.org/0000-0002-5965-1006)
- Eufrânio N. da Silva Júnior (ORCID: https://orcid.org/0000-0003-1281-5453)
- Esther R. S. Paz (ORCID: https://orcid.org/0000-0001-5489-5100)
- Victor F. S. Ramos
Institutions
- Universidade Federal de Minas Gerais (BR)
- University of Liverpool (GB)
- Victoria University of Wellington (NZ)
- Universidade Federal do Espírito Santo (BR)
- Fundação Oswaldo Cruz (BR)
Publication Details
- Journal
- RSC Medicinal Chemistry
- Published
- 2024-09-26
- DOI
- https://doi.org/10.1039/d4md00558a
- Citations
- 3
- Primary Topic
- Bioactive Compounds and Antitumor Agents
- Type
- article
- Field-Weighted Citation Impact
- 1.05
Funders
- Alexander von Humboldt-Stiftung
- Royal Society
- Royal Society of Chemistry
- University of Liverpool
- Coordenação de Aperfeiçoamento de Pessoal de Nível Superior
- Conselho Nacional de Desenvolvimento Científico e Tecnológico
- Fundação de Amparo à Pesquisa do Estado de Minas Gerais
- Fundação de Amparo à Pesquisa e Inovação do Estado de Santa Catarina
- Instituto Nacional de Ciência e Tecnologia de Catálise em Sistemas Moleculares e Nanoestruturados
- Worldwide Universities Network