94-62-2Relevant articles and documents
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.
Identification and optimization of piperine analogues as neuroprotective agents for the treatment of Parkinson's disease via the activation of Nrf2/keap1 pathway
Cai, Xiaoying,Chen, Lijuan,Hong, Feng,Kuang, Shuang,Li, Yan,Ma, Xu,Qi, Wenyan,Shi, Mingsong,Wang, Lun,Xu, Ruiling,Xue, Linlin,Ye, Haoyu,Zhang, Ruijia
, (2020/05/11)
Parkinson's disease (PD) is a slowly progressive and complex neurodegenerative disorder. Up to date, there are no approved drugs that could slow or reverse the neurodegenerative process of PD. Here, we reported the synthesis of series of piperine analogues and the evaluation of their neuroprotective effects against hydrogen peroxide (H2O2) induced damage in the neuron-like PC12 cells. Among these analogues, 3b exhibited the most potent protection effect and its underlying mechanism was further investigated. Further results indicated that the ROS scavenging and cytoprotection effect of 3b might be related to the Nrf2 activation and upregulation of related phase II antioxidant enzymes, such as HO-1 and NQO1. In in vivo study, oral administration (100 mg/kg) of 3b significantly attenuated PD-associated behavioral deficits in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced mouse model of PD and protected tyrosine hydroxylase-immunopositive dopaminergic neurons. Our results provided evidence that 3b might be a promising candidate for Parkinson's disease treatment.
Piperine synthesis method
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, (2019/11/28)
The invention discloses a piperine synthesis method. According to the synthesis method, 5-(1,2-methylenedioxyphenyl)-2-pentenal is taken as the primary raw material; a palladium catalyst is used, oxygen is taken as the oxidizing agent, trifluoroacetic acid is taken as the additive, in a polar organic solvent, one-step oxidation-dehydrogenation is performed to obtain 5-(1,2-methylenedioxyphenyl)-2,4-dipentenal, then oxidation and amidation are carried out to obtain piperine, and the yield is high. The key step namely palladium is used to catalyze oxidation-dehydrogenation is realized, and piperine can be synthesized efficiently and concisely. Compared with a conventional method, the operation is simple, the reaction yield is higher, the method is environmentally friendly, the yield is high,and the atom utilization rate is high.