化学
结构异构体
酶
立体化学
酰肼
IC50型
组合化学
化学合成
体外
有机化学
生物化学
作者
Eun Beul Park,Kwang Jong Kim,Hui Rak Jeong,Jae Kyun Lee,Hyoung Ja Kim,Hwi Ho Lee,Jiwoong Lim,Ji‐Sun Shin,Andreas Koeberle,Oliver Werz,Kyung‐Tae Lee,Jae Yeol Lee
标识
DOI:10.1016/j.bmcl.2016.09.070
摘要
In our previous research, a novel series of phenylsulfonyl hydrazide derivatives were found to reduce LPS-induced PGE2 levels in RAW 264.7 macrophage cells via an inhibition of mPGES-1 enzyme. Recently, it was found that a regioisomeric mixture of phenylsulfonyl hydrazide was formed depending on the reaction conditions, which favor either of two regioisomers. One regioisomer corresponds to a kinetic product (7a-7c) and the other regioisomer corresponds to a thermodynamic product (8a-8c). Among them, the structure of kinetic product 7b was confirmed by measuring single X-ray crystallography. In vitro PGE2 assay studies showed that the kinetic product (7a and 7b; IC50=0.69 and 0.55μM against PGE2) is generally more potent than the thermodynamic product (8a and 8b; IC50=>10 and 0.79μM against PGE2). A molecular docking study also exhibited that the kinetic product (7a) has a higher MolDock Score (-147.4) than that of 8a (-142.4), which is consistent with the PGE2 assay results. A new potent phenylsulfonyl hydrazide (7d; IC50=0.06μM against PGE2) without affecting COX-1 and COX-2 enzyme activities was identified based on these overall results.
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