Bioorganic & Medicinal Chemistry 2009-01-01

Identification of aquaporin 4 inhibitors using in vitro and in silico methods.

Vincent J Huber, Mika Tsujita, Tsutomu Nakada

Index: Bioorg. Med. Chem. 17 , 411-417, (2009)

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Abstract

The in vitro inhibitory effects and in silico docking energies of 18 compounds with respect to aquaporin 4 (AQP4) were investigated. More than half of the compounds tested showed inhibitory activity in the in vitro functional assay and included the 5-HT(1B/1D) agonists sumatriptan, and rizatriptan. Moreover, the observed inhibitory activity of the compounds used in this study at 20 microM showed a strong correlation with their in silico docking energies, r(2)=0.64, which was consistent with that found in previous studies. The AQP4 inhibitory IC(50) values of three compounds, 2-(nicotinamido)-1,3,4-thiadiazole, sumatriptan and rizatriptan, were subsequently found to be 3, 11, and 2 microM, respectively.