Synthesis of N-aryl-5-amino-4-cyanopyrazole derivatives as potent xanthine oxidase inhibitors

• Tipo: Artigo em Revista Científica Internacional
• Data: 2008

Autores

Sanjay Gupta (Autor) Outra; Ligia M Rodrigues (Autor) Outra; Ana P Esteves (Autor) Outra; Ana M F Oliveira Campos (Autor) Outra; Sao S J Jose Nascimento (Autor) FFUP; Nazareth, N (Autor) Outra; Honorina Cidade (Autor) FFUP; Marta P Neves (Autor) Outra; Eduarda Fernandes (Autor) FFUP; Madalena Pinto (Autor) FFUP; Nuno M F S A Cerqueira (Autor) FCUP; Natercia Bras (Autor) Outra

Revista

Título: European Journal of Medicinal Chemistry

Vol. 43 Nº 4

Páginas: 771-780

ISSN: 0223-5234

Editora: Elsevier

Indexação

ISI Web of Knowledge - 88 Citações

Scopus - 98 Citações

Classificação Científica

FOS: Ciências médicas e da saúde > Medicina básica

Outras Informações

ID Authenticus: P-004-0D3

DOI: 10.1016/j.ejmech.2007.06.002

Abstract (EN): Some pyrazolo[3,4-d]pyrimidines, structurally related with allopurinol, a well known xanthine oxidase inhibitor, clinically used in the therapy of gout, have also been reported as potent inhibitors of xanthine oxidase and the growth of several human tumour cell lines. Considering the potential interest of this family of compounds, the aim of the present study was to synthesise and provide a full chemical characterization of new N-aryl-5-amino-4-cyanopyrazole derivatives and their corresponding pyrazolo[3,4-d]pyrimidines. Their biological activity pertaining to the xanthine oxidase inhibition and effect on the growth of three tumour cell lines (MCF-7, NCI-H460, and SF-268) are also provided. With only one exception, the synthesised compounds showed no effect on the growth of the three tumour cell lines. However, a strong xanthine oxidase inhibitory activity was observed for almost all pyrazolo[3,4-d]pyrimidines tested, revealing some of them IC(50) values below 1 mu M. The results of the molecular docking studies of these compounds, against xanthine oxidoreductase are also described, providing an atomistic explanation of the differences in the inhibitory efficiency. MEP calculations were used to explain different inhibitory efficiency of similar inhibitors.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 10