LAUSR

Gliflozins are successfully marketed antidiabetic agents with a reported neuroprotective effect, this study tests their blood-brain barrier crossing ability. Henceforward, a computational hypothesis interpreting their effects was reasonable after failure to cross into the brain. A chromatographic bioassay for Canagliflozin, Dapagliflozin, and Empagliflozin was developed, validated, and applied to the rat's plasma and rat's brain. HPLC method robustness was tested over two levels using Design of Experiment on MINITAB®. It's the first method for gliflozins' detection in rats' brain tissue. The method was applied on eighteen rats, six for each drug. Concentrations in plasma were determined but neither of them was detected in brain at the described chromatographic conditions. A computational study for the three drugs was endorsing two techniques. Firstly, Ligand Based Target Fishing reveals possible targets for gliflozins. They showed an ability to bind with human Equilibrative Nucleoside Transporter 1, a regulator of adenosine extracellularly. Secondly, a docking study was carried out on this protein receptor. Results showed perfect alignment with a minimum of one hydrogen bond. Dapagliflozin achieved the lowest energy score with two hocking hydrogen bonds. This is proposing gliflozins ability to regulate Equilibrative Nucleoside Transporter 1 receptors in peripheries, elevating the centrally acting neuroprotective adenosine. This article is protected by copyright. All rights reserved.