Action of Clathrodin and Analogues on Voltage-Gated Sodium Channels

Marine Drugs

Steve Peigneur²  Aleš Žula³  Nace Zidar³  Fiona Chan-Porter¹  Robert Kirby¹  David Madge¹  Janez Ilaš³  Danijel Kikelj³ 

[1] Xention Ltd., Iconix Park, London Road, Pampisford, Cambridge CB22 3EG, UK; E-Mails:;Catholic University Leuven (KULeuven), Toxicology and Pharmacology, Herestraat 49-Box 922, 3000 Leuven, Belgium; E-Mail:;University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000 Ljubljana, Slovenia; E-Mails:

关键词: clathrodin;    oroidin;    hymenidin;    voltage-gated sodium channels;    sodium channel modulator;    sponge;   

DOI  :  10.3390/md12042132

来源: mdpi

【 摘 要 】

Clathrodin is a marine alkaloid and believed to be a modulator of voltage-gated sodium (Na_V ) channels. Since there is an urgent need for small molecule Na_V channel ligands as novel therapeutics, clathrodin could represent an interesting lead compound. Therefore, clathrodin was reinvestigated for its potency and Na_V channel subtype selectivity. Clathrodin and its synthetic analogues were subjected to screening on a broad range of Na_V channel isoforms, both in voltage clamp and patch clamp conditions. Even though clathrodin was not found to exert any activity, some analogues were capable of modulating the Na_V channels, hereby validating the pyrrole-2-aminoimidazole alkaloid structure as a core structure for future small molecule-based Na_V channel modulators.

【 授权许可】

CC BY   
© 2014 by the authors; licensee MDPI, Basel, Switzerland.