Phenolic hydrazones are potent inhibitors of macrophage migration inhibitory factor proinflammatory activity and survival improving agents in sepsis

被引：56

作者：

Dabideen, Darrin R.

Cheng, Kai Fan

Aljabari, Bayan

Miller, Edmund J.

Pavlov, Valentin A.

Al-Abed, Yousef

机构：

[1] Feinstein Inst Med Res, Med Chem Lab, Manhasset, NY 11030 USA

[2] Feinstein Inst Med Res, Lab Cardiopulm Res, Manhasset, NY 11030 USA

[3] Feinstein Inst Med Res, Lab Biomed Sci, Manhasset, NY 11030 USA

[4] NYU, Sch Med, New York, NY 10016 USA

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2007年 / 50卷 / 08期

关键词：

D O I：

10.1021/jm061477+

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

A series of phenolic hydrazones were synthesized and evaluated for their inhibition of macrophage migration inhibitory factor (MIF) tautomerase activity. Compound 7 emerged as a potent inhibitor of MIF with an IC50 of 130 nM. Compound 7 dose-dependently suppressed TNF alpha secretion from lipopolysaccharide stimulated macrophages. The therapeutic importance of the MIF inhibition by 7 is demonstrated by the significant protection from the lethality of sepsis when administration of the compound was initiated in a clinically relevant time frame.

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页码：1993 / 1997

页数：5

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