Novel Meroterpenoids from <i>Hypericum patulum</i>: Highly Potent Late Na<sub>v</sub>1.5 Sodium Current Inhibitors
Yan-Song Ye, Shuzong Du, Nana Jiang, Hong‐Xi Xu, Jian Yang, Wenwei Fu, Yin Nian, Gang Xu
Abstract
Hypulatones A and B (1 and 2), two racemic meroterpenoids possessing an unprecedented spiro[benzofuran-2,1′-cycloundecan]-4′-ene-4,6(5H)-dione core, were characterized from Hypericum patulum. Compound 2 was found to significantly inhibit the late current of Nav1.5 (late INa, IC50 = 0.2 μM). Importantly, 2 exhibited remarkable separation (>100-fold) of late INa relative to peak INa and notable selectivity over Cav3.1, Kv1.5, and hERG. 1 showed comparable inhibition on late INa compared to that of 2 with poorer selectivity.
Topics & Concepts
ChemistrySelectivityStereochemistryNav1.5BenzofuranIC50SodiumSodium channelBiochemistryOrganic chemistryIn vitroCatalysisNatural Compound Pharmacology StudiesSynthesis of Organic CompoundsBioactive Compounds and Antitumor Agents