Chiral Derivatives of Xanthones: Investigation of the Effect of Enantioselectivity on Inhibition of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

• Tipo: Artigo em Revista Científica Internacional
• Data: 2017

Autores

Fernandes, C (Autor) Outra; Palmeira, A (Autor) Outra; Ramos, II (Autor) Outra; Carneiro, C (Autor) Outra; Carlos Afonso (Autor) FFUP; M E Tiritan (Autor) FFUP; Honorina Cidade (Autor) FFUP; Pinto, PCAG (Autor) Outra; Lucia L M F S Saraiva (Autor) FFUP; Salette Reis (Autor) FFUP; Pinto, MMM (Autor) Outra; Carla Fernandes (Autor) FFUP

Revista

Título: Pharmaceuticals

Vol. 10

Página Final: 50

ISSN: 1424-8247

Editora: MDPI

Indexação

ISI Web of Knowledge - 25 Citações

Scopus - 26 Citações

Outras Informações

ID Authenticus: P-00N-2BR

DOI: 10.3390/ph10020050

Abstract (EN): Searching of new enantiomerically pure chiral derivatives of xanthones (CDXs) with potential pharmacological properties, particularly those with anti-inflammatory activity, has remained an area of interest of our group. Herein, we describe in silico studies and in vitro inhibitory assays of cyclooxygenases (COX-1 and COX-2) for different enantiomeric pairs of CDXs. The evaluation of the inhibitory activities was performed by using the COX Inhibitor Screening Assay Kit. Docking simulations between the small molecules (CDXs; known ligands and decoys) and the enzyme targets were undertaken with AutoDock Vina embedded in PyRx-Virtual Screening Tool software. All the CDXs evaluated exhibited COX-1 and COX-2 inhibition potential as predicted. Considering that the (S)-(-)-enantiomer of the nonsteroidal anti-inflammatory drug ketoprofen preferentially binds to albumin, resulting in lower free plasma concentration than (R)-(+)-enantiomer, protein binding affinity for CDXs was also evaluated by spectrofluorimetry as well as in in silico. For some CDXs enantioselectivity was observed.

Idioma: Inglês

Tipo (Avaliação Docente): Científica

Nº de páginas: 13