Chiral Derivatives of Xanthones: Investigation of Enantioselectivity as Inhibitors of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

Carla Fernandes; Andreia Palmeira; Inês Ramos; Carlos Carneiro; Carlos Afonso; Maria Tiritan; Honorina Cidade; Paula Pinto; M. Lúcia Saraiva; Salette Reis; Madalena Pinto

doi:10.3390/ecmc-2-A023

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Chiral Derivatives of Xanthones: Investigation of Enantioselectivity as Inhibitors of Cyclooxygenases (COX-1 and COX-2) and Binding Interaction with Human Serum Albumin

^{1, 2},

^{1, 2},

¹,

¹,

^{1, 2},

Maria Elizabeth Tiritan

^{1, 2, 3},

Honorina Cidade

^{1, 2},

Paula C.A.G. Pinto

⁴,

M. Lúcia M.F.S. Saraiva

⁴,

Salette Reis

⁴,

Madalena Pinto

^{*

1, 2}

¹ 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
² 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
³ CESPU, Instituto de Investigação e Formação Avançada em Ciências e Tecnologias da Saúde, Rua Central de Gandra, 1317, 4585-116 Gandra PRD, Portugal
⁴ REQUIMTE, Departamento de Ciências Químicas, Faculdade de Farmácia, Universidade do Porto, Rua de Jorge Viterbo Ferreira, 228, 4050 313 Porto, Portugal

Published: 01 November 2016 by MDPI in 2nd International Electronic Conference on Medicinal Chemistry session ECMC-2

https://doi.org/10.3390/ecmc-2-A023

Abstract:

Searching for new enantiomerically pure chiral derivatives of xanthones (CDXs) with potential pharmacological properties has remained an area of interest of our group, namely those with anti-inflammatory activity [1,2]. Herein, we describe in silico studies and in vitro inhibitory assays of different enantiomeric pairs of CDXs. The evaluation of the inhibition of cyclooxygenases (COX-1 and COX-2) 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 [3], protein binding affinity for CDXs was also evaluated by spectrofluorimetry. For some CDXs enantioselectivity was observed.

[1] Fernandes, C., et al. Bioorg Med Chem. 2014, 22(3), 1049-1062.

[2] Fernandes, C., et al. Eur. J. Med. Chem. 2012, 55, 1-11.

[3] Evans, S. E. et al. Trends in Environmental Analytical Chemistry, 2014, 1(0), e34-e51.

This research was partially supported by the Structured Program of R&D&I INNOVMAR –Innovation and Sustainability in the Management and Exploitation of Marine Resources (reference NORTE-01-0145-FEDER-000035, Research Line NOVELMAR), funded by the Northern Regional Operational Programme (NORTE2020) through the European Regional Development Fund (ERDF) and by Foundation for Science and Technology (FCT) and COMPETE under the projects PTDC/MAR-BIO/4694/2014 (POCI-01-0145-FEDER-016790) and COXANT–CESPU- 2016.

Keywords: Chiral derivatives of xanthones; Cyclooxiganase; Albumin

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