Anesthetic potency of two novel synthetic polyhydric alkanols longer than the n-alkanol cutoff:: Evidence for a bilayer-mediated mechanism of anesthesia?
Anesthetic potency of two novel synthetic polyhydric alkanols longer than the n-alkanol cutoff:: Evidence for a bilayer-mediated mechanism of anesthesia?
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DOI：
10.1021/jm049459k
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发表时间：
2005-06-16
影响因子：
7.3
通讯作者：
Cantor, RS
中科院分区：
文献类型：
--
作者：
Mohr, JT;Gribble, GW;Cantor, RS
利用噻吩环作为骨架，通过酸性α-氢的锂化和随后的脱硫，合成了多羟基烷烃1，6，11，16-十六烷四醇（1）和2，7，12，17-十八烷四醇（2）。这两种化合物表现出显着的麻醉效力，单独和与己醇的加和性研究，使用蝌蚪的不动性作为表型终点。这些结果，这与蛋白质结合机制，其中截断结果从空间位阻矛盾，是一致的，与最近的预测膜介导的机制，涉及侧压力分布。
The polyhydroxyalkanes 1,6,11,16-hexadecanetetraol (1) and 2,7,12,17-octadecanetetraol (2) were synthesized utilizing the thiophene ring as a scaffold to affix the hydroxyalkyl chains by lithiation of the acidic alpha-hydrogens and subsequent desulfurization. Both compounds exhibited significant anesthetic potency, individually and in additivity studies with hexanol, using immobility in tadpoles as the phenotypic endpoint. These results, which contradict a protein-binding mechanism in which cutoff results from steric hindrance, are consistent with recent predictions of a membrane-mediated mechanism involving the lateral pressure profile.