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

• Autor(a) principal: Fernandes C.
• Data de Publicação: 2017
• Outros Autores: Palmeira A., Ramos I.I., Carneiro C., Afonso C., Tiritan M.E., Cidade H., Pinto P.C.A.G., Saraiva M.L.M.F.S., Reis S., Pinto M.M.M.
• Tipo de documento: Artigo
• Idioma: eng
• Título da fonte: Repositório Científico de Acesso Aberto de Portugal (Repositórios Cientìficos)
• Texto Completo: https://hdl.handle.net/10216/120430
• topic: albumin; azapropazone; celecoxib; cyclooxygenase 1; cyclooxygenase 2; diazepam; diclofenac; fusidic acid; ibuprofen; indometacin; iophenoxic acid; ketoprofen; naproxen; piroxicam; valdecoxib; warfarin; xanthone derivative; albumin blood level; Article; binding affinity; chirality; computer model; controlled study; drug mechanism; drug protein binding; drug structure; enantioselectivity; enzyme inhibition; fluorescence; human; immunoassay; ligand binding; molecular docking; protein protein interaction; spectrofluorometry

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. © 2017 by the authors. Licensee MDPI, Basel, Switzerland.