Abstract
The potential of antiepileptic drugs (AEDs) to inhibit the water transport properties of Aquaporin 4 (AQP4) was investigated using a combination of in silico and in vitro screening methods. Virtual docking studies on 14 AEDs indicated a range of docking energies that spanned approximately 40 kcal/mol, where the most stabilized energies were consistent with that of the previously identified AQP4 inhibitor acetazolamide. Nine AEDs and one bio-active metabolite were further investigated in a functional assay using AQP4 expressing Xenopus oocytes. Seven of the assayed compounds were found to inhibit AQP4 function, while three did not. A linear correlation was indicated between the in silico docking energies and the in vitro AQP4 inhibitory activity at 20 μM.
Original language | English (US) |
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Pages (from-to) | 418-424 |
Number of pages | 7 |
Journal | Bioorganic and Medicinal Chemistry |
Volume | 17 |
Issue number | 1 |
DOIs | |
State | Published - Jan 1 2009 |
Keywords
- Antiepileptic drugs
- Aquaporin
- Aquaporin 4
- Drug design
- Xenopus laevis oocytes
ASJC Scopus subject areas
- Pharmaceutical Science
- Drug Discovery
- Organic Chemistry
- Molecular Medicine
- Molecular Biology
- Clinical Biochemistry
- Biochemistry