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

• Main Authors: Carla Fernandes (Author), Andreia Palmeira (Author), Inês I. Ramos (Author), Carlos Carneiro (Author), Carlos Afonso (Author), Maria Elizabeth Tiritan (Author), Honorina Cidade (Author), Paula C.A.G. Pinto (Author), M. Lúcia M.F.S. Saraiva (Author), Salette Reis (Author), Madalena M.M. Pinto (Author)
• Format: Book
• Published: MDPI AG, 2017-05-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.

Summary

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.

Item Description

1424-8247
10.3390/ph10020050