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

• Type: Article in International Scientific Journal
• Date: 2008

Authors

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

Journal

Title: European Journal of Medicinal Chemistry

Vol. 43 No. 4

Pages: 771-780

ISSN: 0223-5234

Publisher: Elsevier

Indexing

ISI Web of Knowledge - 88 Citations

Scopus - 98 Citations

Scientific classification

FOS: Medical and Health sciences > Basic medicine

Other information

Authenticus ID: 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.

Language: English

Type (Professor's evaluation): Scientific

No. of pages: 10