他莫昔芬对膜甾醇的结构模拟：来自胆固醇系数及分子建模的证据，证明其作为膜抗氧化剂和抗癌剂的作用。

The structural mimicry of membrane sterols by tamoxifen: evidence from cholesterol coefficients and molecular-modelling for its action as a membrane anti-oxidant and an anti-cancer agent.

作者信息

Wiseman H, Cannon M, Arnstein H R, Barlow D J

机构信息

Department of Biochemistry, King's College London, U.K.

出版信息

Biochim Biophys Acta. 1992 Mar 20;1138(3):197-202. doi: 10.1016/0925-4439(92)90038-o.

DOI:10.1016/0925-4439(92)90038-o

PMID:1547281

Abstract

The anti-cancer drug tamoxifen is a potent inhibitor of lipid peroxidation induced by Fe(III)-ascorbate in ox-brain phospholipid liposomes. Similar anti-oxidant effects, but with varying potencies, are also shown by 4-hydroxy-tamoxifen, cholesterol, ergosterol and 17-beta-oestradiol. We now describe a computer-graphic fitting technique that demonstrates a structural similarity between the five compounds. In addition, we have quantified the differences (relative to cholesterol) between the anti-oxidant activities of the compounds in terms of a novel expression referred to here as the cholesterol coefficient (Cc) Finally, we discuss how the inhibitory effect of tamoxifen on lipid peroxidation may result from a membrane stabilization that is associated with a decrease in membrane fluidity. This action may be related to the anti-proliferative effect exerted by tamoxifen on cancer and fungal cells.

摘要

抗癌药物他莫昔芬是铁（III）-抗坏血酸诱导的牛脑磷脂脂质体脂质过氧化的有效抑制剂。4-羟基他莫昔芬、胆固醇、麦角固醇和17-β-雌二醇也表现出类似的抗氧化作用，但效力不同。我们现在描述一种计算机图形拟合技术，该技术证明了这五种化合物之间的结构相似性。此外，我们根据一种新的表达式（这里称为胆固醇系数（Cc））对这些化合物的抗氧化活性与胆固醇之间的差异进行了量化。最后，我们讨论了他莫昔芬对脂质过氧化的抑制作用可能是如何由与膜流动性降低相关的膜稳定作用导致的。这种作用可能与他莫昔芬对癌细胞和真菌细胞的抗增殖作用有关。