期刊
BIOORGANIC & MEDICINAL CHEMISTRY
卷 22, 期 4, 页码 1276-1284出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.bmc.2014.01.008
关键词
Pholidota chinensis; HPLC-based activity profiling; GABA(A) receptor modulators; Dihydrostilbenes
资金
- Swiss National Science Foundation [205320_126888]
- Swiss Federal Commission
- Department of Education of Canton Basel (Erziehungsdepartement des Kantons Basel-Stadt)
- Swiss National Science Foundation (SNF) [205320_126888] Funding Source: Swiss National Science Foundation (SNF)
A dichloromethane extract of stems and roots of Pholidota chinensis (Orchidaceae) enhanced GABA-induced chloride currents (I-GABA) by 132.75 +/- 36.69% when tested at 100 mu g/mL in a two-micro-electrode voltage clamp assay, on Xenopus laevis oocytes expressing recombinant alpha(1)beta(2)gamma S-2 GABA(A) receptors. By means of an HPLC-based activity profiling approach, the three structurally related stilbenoids coelonin (1), batatasin III (2), and pholidotol D (3) were identified in the active fractions of the extract. Dihydrostilbene 2 enhanced I-GABA by 1512.19 +/- 176.47% at 300 mu M, with an EC50 of 52.51 +/- 16.96 mu M, while compounds 1 and 3 showed much lower activity. The relevance of conformational flexibility for receptor modulation by stilbenoids was confirmed with a series of 13 commercially available stilbenes and their corresponding semisynthetic dihydro derivatives. Dihydrostilbenes showed higher activity in the oocyte assay than their corresponding stilbenes. The dihydro derivatives of tetramethoxy-piceatannol (12) and pterostilbene (20) were the most active among these derivatives, but they showed lower efficiencies than compound 2. Batatasin III (2) showed high efficiency but no significant subunit specificity when tested on the receptor subtypes alpha(1)beta(2)gamma(2)s, alpha(2)beta(2)gamma(2)s, alpha(3)beta(2)gamma(2)s, alpha(4)beta(2)gamma(2)s, alpha(5)beta(2)gamma(2)s, alpha(1)beta(1)gamma(2)s, and alpha(1)beta(3)gamma(2)s. Dihydrostilbenes represent a new scaffold for GABAA receptor modulators. (C) 2014 Elsevier Ltd. All rights reserved.
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