Inhibition of Aquaporin 4 by antiepileptic drugs

Vincent J. Huber; Mika Tsujita; Ingrid Kwee; Tsutomu Nakada

doi:10.1016/j.bmc.2007.12.038

Inhibition of Aquaporin 4 by antiepileptic drugs

Vincent J. Huber, Mika Tsujita, Ingrid Kwee, Tsutomu Nakada

Neurology

Research output: Contribution to journal › Article › peer-review

88 Scopus citations

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)
Pages (from-to)	418-424
Number of pages	7
Journal	Bioorganic and Medicinal Chemistry
Volume	17
Issue number	1
DOIs	https://doi.org/10.1016/j.bmc.2007.12.038
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

Access to Document

10.1016/j.bmc.2007.12.038

Fingerprint Dive into the research topics of 'Inhibition of Aquaporin 4 by antiepileptic drugs'. Together they form a unique fingerprint.

Cite this

@article{00345807742c421cb2c1169dd276fd17,

title = "Inhibition of Aquaporin 4 by antiepileptic drugs",

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.",

keywords = "Antiepileptic drugs, Aquaporin, Aquaporin 4, Drug design, Xenopus laevis oocytes",

author = "Huber, {Vincent J.} and Mika Tsujita and Ingrid Kwee and Tsutomu Nakada",

year = "2009",

month = jan,

day = "1",

doi = "10.1016/j.bmc.2007.12.038",

language = "English (US)",

volume = "17",

pages = "418--424",

journal = "Bioorganic and Medicinal Chemistry",

issn = "0968-0896",

publisher = "Elsevier Limited",

number = "1",

}

TY - JOUR

T1 - Inhibition of Aquaporin 4 by antiepileptic drugs

AU - Huber, Vincent J.

AU - Tsujita, Mika

AU - Kwee, Ingrid

AU - Nakada, Tsutomu

PY - 2009/1/1

Y1 - 2009/1/1

N2 - 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.

AB - 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.

KW - Antiepileptic drugs

KW - Aquaporin

KW - Aquaporin 4

KW - Drug design

KW - Xenopus laevis oocytes

UR - http://www.scopus.com/inward/record.url?scp=57649234535&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=57649234535&partnerID=8YFLogxK

U2 - 10.1016/j.bmc.2007.12.038

DO - 10.1016/j.bmc.2007.12.038

M3 - Article

C2 - 18178093

AN - SCOPUS:57649234535

VL - 17

SP - 418

EP - 424

JO - Bioorganic and Medicinal Chemistry

JF - Bioorganic and Medicinal Chemistry

SN - 0968-0896

IS - 1

ER -