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Novel Meroterpenoids from Hypericum patulum: Highly Potent Late Nav1.5 Sodium Current Inhibitors
Yan-Song Ye1,2, Shu-Zong Du3,2, Na-Na Jiang1,2
1State Key Laboratory of Phytochemistry and Plant Resources in West China and Yunnan Key Laboratory of Natural Medicinal Chemistry, Kunming Institute of Botany, Chinese Academy of Sciences, Kunming 650201, People's Republic of China.
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.
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