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

Laboratório de Química Orgânica e Farmacêutica, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua Jorge Viterbo Ferreira nº 228, 4050-313 Porto, Portugal

Centro Interdisciplinar de Investigação Marinha e Ambiental (CIIMAR), Universidade do Porto, Edifício do Terminal de Cruzeiros do Porto de Leixões, Av. General Norton de Matos s/n, 4050-208 Matosinhos, Portugal

CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra 1317, 4585-116 Gandra PRD, Portugal

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REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050‑313 Porto, Portugal

Author to whom correspondence should be addressed.

Academic Editor: Jean Jacques Vanden Eynde

Pharmaceuticals 2017, 10(2), 50; https://doi.org/10.3390/ph10020050

Received: 22 April 2017 / Revised: 25 May 2017 / Accepted: 27 May 2017 / Published: 31 May 2017

(This article belongs to the Special Issue Selected Papers from the 2nd International Electronic Conference on Medicinal Chemistry)

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Abstract

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. View Full-Text

Keywords: chiral derivatives of xanthones; cyclooxygenase; albumin; enantioselectivity; docking

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MDPI and ACS Style

Fernandes, C.; 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. 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. Pharmaceuticals 2017, 10, 50. https://doi.org/10.3390/ph10020050

AMA Style

Fernandes C, Palmeira A, Ramos II, Carneiro C, Afonso C, Tiritan ME, Cidade H, Pinto PCAG, Saraiva MLMFS, Reis S, Pinto MMM. 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. Pharmaceuticals. 2017; 10(2):50. https://doi.org/10.3390/ph10020050

Chicago/Turabian Style

Fernandes, Carla, Andreia Palmeira, Inês I. Ramos, Carlos Carneiro, Carlos Afonso, Maria E. Tiritan, Honorina Cidade, Paula C.A.G. Pinto, M. L.M.F.S. Saraiva, Salette Reis, and Madalena M.M. Pinto. 2017. "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" Pharmaceuticals 10, no. 2: 50. https://doi.org/10.3390/ph10020050

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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

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