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氟奋乃静-芥子气(一种不可逆的钙调蛋白拮抗剂)的药理学特性。

Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist.

作者信息

Hait W N, Glazer L, Kaiser C, Cross J, Kennedy K A

机构信息

Department of Internal Medicine and Pharmacology, Yale University School of Medicine, New Haven, Connecticut.

出版信息

Mol Pharmacol. 1987 Sep;32(3):404-9.

PMID:3670276
Abstract

We describe an improved synthesis and properties of fluphenazine-mustard, a potent phenothiazine having an alkylating chlorethylamine chain in its structure. The drug possesses anticalmodulin activity equivalent to the parent compound, but unlike fluphenazine dihydrochloride, the mustard derivative irreversibly antagonizes the ability of calmodulin to activate cyclic nucleotide phosphodiesterase. This property is partially calcium-dependent and can be overcome by coincubation with excess fluphenazine dihydrochloride. The compound irreversibly inactivated calmodulin when incubated with intact cells and caused single-stranded breakage of DNA. Fluphenazine-mustard possesses potent antiproliferative and cytotoxic properties against malignant cell lines that are likely to be mediated through both of these actions.

摘要

我们描述了氟奋乃静氮芥的一种改进合成方法及其性质,氟奋乃静氮芥是一种强效吩噻嗪,其结构中含有一个烷基化氯乙胺链。该药物具有与母体化合物相当的抗钙调蛋白活性,但与盐酸氟奋乃静不同的是,氮芥衍生物不可逆地拮抗钙调蛋白激活环核苷酸磷酸二酯酶的能力。这一特性部分依赖于钙,并且可以通过与过量的盐酸氟奋乃静共同孵育来克服。当与完整细胞一起孵育时,该化合物会不可逆地使钙调蛋白失活,并导致DNA单链断裂。氟奋乃静氮芥对恶性细胞系具有强大的抗增殖和细胞毒性,可能是通过这两种作用介导的。

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Pharmacological properties of fluphenazine-mustard, an irreversible calmodulin antagonist.氟奋乃静-芥子气(一种不可逆的钙调蛋白拮抗剂)的药理学特性。
Mol Pharmacol. 1987 Sep;32(3):404-9.
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