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.