67629-62-3Relevant articles and documents
Stereoselective ozonolysis of TMS-substituted allylic alcohol derivatives and synthesis of 14R,15 S - And 14 S,15 S-diHETE
Saito, Shun,Yamazaki, Takashi,Kobayashi, Yuichi
, p. 7636 - 7647 (2018)
Ozonolysis of TMS-substituted olefins produces α-carbonyl TMS peroxides without cleavage of the CC bond. Herein, stereochemistry in the ozonolysis was studied using silyl derivatives of (E)- and (Z)-(1-TMS)alk-1-en-3-ols. The (E)-isomers afforded the anti-3-siloxy-2-(TMS-oxy)aldehydes as the major stereoisomer (anti/syn = 3-9:1) after reductive work-up with Ph3P. In contrast, Z-olefins selectively gave the syn isomers with syn/anti ratios of 4-19:1. Facial selection was speculated based on the Cieplak effect. This ozonolysis was successfully applied for the synthesis of 14R,15S- and 14S,15S-diHETEs (anti and syn isomers, respectively) in enantioenriched forms.
The development of novel cytochrome P450 2J2 (CYP2J2) inhibitor and the underlying interaction between inhibitor and CYP2J2
Tian, Xiangge,Zhou, Meirong,Ning, Jing,Deng, Xiaopeng,Feng, Lei,Huang, Huilian,Yao, Dahong,Ma, Xiaochi
, p. 737 - 748 (2021/03/16)
Human Cytochrome P450 2J2 (CYP2J2) as an important metabolic enzyme, plays a crucial role in metabolism of polyunsaturated fatty acids (PUFAs). Elevated levels of CYP2J2 have been associated with various types of cancer, and therefore it serves as a potential drug target. Herein, using a high-throughput screening approach based on enzymic activity of CYP2J2, we rapidly and effectively identified a novel natural inhibitor (Piperine, 9a) with IC50 value of 0.44 μM from 108 common herbal medicines. Next, a series of its derivatives were designed and synthesised based on the underlying interactions of Piperine with CYP2J2. As expected, the much stronger inhibitors 9k and 9l were developed and their inhibition activities increased about 10 folds than Piperine with the IC50 values of 40 and 50 nM, respectively. Additionally, the inhibition kinetics illustrated the competitive inhibition types of 9k and 9l towards CYP2J2, and K i were calculated to be 0.11 and 0.074 μM, respectively. Furthermore, the detailed interaction mechanism towards CYP2J2 was explicated by docking and molecular dynamics, and our results revealed the residue Thr114 and Thr 315 of CYP2J2 were the critical sites of action, moreover the spatial distance between the carbon atom of ligand methylene and Fe atom of iron porphyrin coenzyme was the vital interaction factor towards human CYP2J2.
A NIR fluorescent probe for fatty acid amide hydrolase bioimaging and its application in development of inhibitors
Deng, Sa,Feng, Lei,Huo, Xiaokui,Ma, Xiaochi,Ning, Jing,Tian, Manman,Tian, Xiangge,Tian, Zhenhao,Wang, Chao,Yao, Dahong,Yu, Zhenlong,Zhang, Baojing
supporting information, p. 6460 - 6465 (2021/08/24)
Fatty acid amide hydrolase (FAAH) is primarily responsible for the inactivation of fatty acid ethanolamide (FAE) and is involved in a variety of biological functions related to diseases of the nervous system. Herein, we developed a highly selective and sensitive FAAH-activated near-infrared fluorescent probe named DAND and achieved the real-time detection and imaging of FAAH activity in complex biosystems. Moreover, a visual high-throughput screening method was established using DAND, piperine was identified as a novel inhibitor of FAAH. Based on the interaction of piperine with FAAH, a more potent FAAH inhibitor (11f) was designed and synthesized which possessed an IC50 value of 0.65 μM. Furthermore, 11f could attenuate the liposaccharide (LPS)-induced activation of BV2 cells, exhibiting an excellent anti-inflammatory activity. These results indicated that DAND could be used as a promising molecular tool for exploring FAAH activity and for rapidly screening potential FAAH inhibitors. In addition, piperine and its derivatives could serve as potential candidate drugs for the treatment of neurodegenerative diseases in the future.
