Terpenoids with vasorelaxant effects from the Chinese liverwort Scapania carinthiaca.

Publisher: Elsevier Science Country of Publication: England NLM ID: 9413298 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1464-3391 (Electronic) Linking ISSN: 09680896 NLM ISO Abbreviation: Bioorg Med Chem Subsets: MEDLINE

Publication: Oxford : Elsevier Science
Original Publication: Oxford : New York : Pergamon Press, c1993-

Antineoplastic Agents, Phytogenic/*pharmacology ; Blood Vessels/*drug effects ; Hepatophyta/*chemistry ; Terpenes/*pharmacology ; Vasodilation/*drug effects ; Vasodilator Agents/*pharmacology; Animals ; Antineoplastic Agents, Phytogenic/chemistry ; Antineoplastic Agents, Phytogenic/isolation & purification ; Cell Line, Tumor ; Cell Proliferation/drug effects ; China ; Dose-Response Relationship, Drug ; Drug Screening Assays, Antitumor ; Humans ; Molecular Conformation ; Rats ; Rats, Wistar ; Structure-Activity Relationship ; Terpenes/chemistry ; Terpenes/isolation & purification ; Vasodilator Agents/chemistry ; Vasodilator Agents/isolation & purification

Four new diterpenoids scapanacins A-D (1-4) including one kaurane and three clerodane derivatives, along with eleven known compounds (9-15), were isolated from the Chinese liverwort Scapania carinthiaca J.B. Jack ex Lindb. Their structures were determined based on extensive spectroscopic analyses, and electronic circular dichroism (ECD) calculations. Vasorelaxant activity assays of the clerodane-type diterpenoids 2, and 4-8 revealed that they relaxed 3 ^rd -order rat mesenteric arterioles pre-contracted with norepinephrine (NE). Further assays with scapanacin D (4) confirmed that the vasodilatation was mediated through inhibition of Ca ²⁺ influx via voltage-dependent Ca ²⁺ channels (VDCs), and this Ca ²⁺ channel blocking effect was also confirmed by inhibiting the extracellular Ca ²⁺ influx in MOVAS cells. Besides, very little decrease of the relaxant activity caused by 4 on endothelium-denuded mesenteric arterioles with NE also suggested the vasodilatation was mainly produced by inhibiting Ca ²⁺ -induced contraction of smooth muscle. In addition, cytotoxicity testing showed that compounds 1 and 9 with α,β-unsaturated ketone exhibited inhibitory activities against a small panel of human cancer cell lines.
(Copyright © 2018 Elsevier Ltd. All rights reserved.)

Keywords: Calcium influx; Clerodanes; Liverworts; Terpenoids; Vasorelaxant

0 (Antineoplastic Agents, Phytogenic)
0 (Terpenes)
0 (Vasodilator Agents)

Date Created: 20180728 Date Completed: 20190204 Latest Revision: 20190215

20231215

10.1016/j.bmc.2018.07.035

30049584