HPLC-Based Activity Profiling for GABAA Receptor Modulators in Searsia pyroides Using a Larval Zebrafish Locomotor Assay

Moradi-Afrapoli, Fahimeh and van der Merve, Hannes and De Mieri, Maria and Wilhelm, Anke and Stadler, Marco and Zietsman, Pieter C. and Hering, Steffen and Swart, Kenneth and Hamburger, Matthias. (2017) HPLC-Based Activity Profiling for GABAA Receptor Modulators in Searsia pyroides Using a Larval Zebrafish Locomotor Assay. Planta Medica, 83 (14/15). pp. 1169-1175.

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Official URL: http://edoc.unibas.ch/56581/

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A dichloromethane extract from leaves of Searsia pyroides potentiated gamma aminobutyric acid-induced chloride currents by 171.8 ± 54% when tested at 100 µg/mL in Xenopus oocytes transiently expressing gamma aminobutyric acid type A receptors composed of α 1 β 2 γ 2s subunits. In zebrafish larvae, the extract significantly lowered pentylenetetrazol-provoked locomotion when tested at 4 µg/mL. Active compounds of the extract were tracked with the aid of HPLC-based activity profiling utilizing a previously validated zebrafish larval locomotor activity assay. From two active HPLC fractions, compounds 1 – 3 were isolated. Structurally related compounds 4 – 6 were purified from a later eluting inactive HPLC fraction. With the aid of 1H and 13C NMR and high-resolution mass spectrometry, compounds 1 – 6 were identified as analogues of anacardic acid. Compounds 1 – 3 led to a concentration-dependent decrease of pentylenetetrazol-provoked locomotion in the zebrafish larvae model, while 4 – 6 were inactive. Compounds 1 – 3 enhanced gamma aminobutyric acid-induced chloride currents in Xenopus oocytes in a concentration-dependent manner, while 4 – 6 only showed marginal enhancements of gamma aminobutyric acid-induced chloride currents. Compounds 2, 3, and 5 have not been reported previously.
Faculties and Departments:05 Faculty of Science > Departement Pharmazeutische Wissenschaften > Pharmazie > Pharmazeutische Biologie (Hamburger)
UniBasel Contributors:Hamburger, Matthias and Moradiafrapoli, Fahimeh and de Mieri, Maria
Item Type:Article, refereed
Article Subtype:Research Article
Publisher:Georg Thieme Verlag
Note:Publication type according to Uni Basel Research Database: Journal article
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Last Modified:09 May 2018 06:48
Deposited On:09 May 2018 06:48

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