Click here to close Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly. We suggest using a current version of Chrome, FireFox, or Safari.
Eur J Med Chem. October 20, 2017; 139 232-241.

Clathrodin, hymenidin and oroidin, and their synthetic analogues as inhibitors of the voltage-gated potassium channels.

Zidar N , Žula A , Tomašič T , Rogers M , Kirby RW , Tytgat J , Peigneur S , Kikelj D , Ilaš J , Mašič LP .

We have prepared three alkaloids from the Agelas sponges, clathrodin, hymenidin and oroidin, and a series of their synthetic analogues, and evaluated their inhibitory effect against six isoforms of the Kv1 subfamily of voltage-gated potassium channels, Kv1.1-Kv1.6, expressed in Chinese Hamster ovary (CHO) cells using automated patch clamp electrophysiology assay. The most potent inhibitor was the (E)-N-(3-(2-amino-1H-imidazol-4-yl)allyl)-4,5-dichloro-1H-pyrrole-2-carboxamide (6g) with IC50 values between 1.4 and 6.1 μM against Kv1.3, Kv1.4, Kv1.5 and Kv1.6 channels. All compounds tested displayed selectivity against Kv1.1 and Kv1.2 channels. For confirmation of their activity and selectivity, compounds were additionally evaluated in the second independent system against Kv1.1-Kv1.6 and Kv10.1 channels expressed in Xenopus laevis oocytes under voltage clamp conditions where IC50 values against Kv1.3-Kv1.6 channels for the most active analogues (e.g. 6g) were lower than 1 μM. Because of the observed low sub-micromolar IC50 values and fairly low molecular weights, the prepared compounds represent good starting points for further optimisation towards more potent and selective voltage-gated potassium channel inhibitors.

PubMed ID: 28802123
Article link: Eur J Med Chem.

External Resources:

Xenbase: The Xenopus laevis and X. tropicalis resource.
Version: 4.9.1
Major funding for Xenbase is provided by the National Institute of Child Health and Human Development, grant P41 HD064556