20697-04-5Relevant articles and documents
Synthesis, characterization and crystal structure of a novel tetranuclear oxidovanadium(V) complex derived from N’-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazide with catalytic property
Qian, Heng-Yu,You, Zhonglu,Zhang, Li
, (2022/03/07)
A novel tetranuclear oxidovanadium(V) complex, [V4O4(OEt)4L4], where L is the dianionic form of N’-(2-hydroxy-3-methoxybenzylidene)isonicotinohydrazide (H2L), has been prepared and characterized by physico-chemical methods and single crystal X-ray diffraction. The V atom in the complex is coordinated by the phenolate oxygen, imino nitrogen and enolate oxygen of one aroylhydrazone ligand, one pyridine nitrogen of another aroylhydrazone ligand, one deprotonated ethanol oxygen, and one oxo group, forming an octahedral coordination. The oxidation of olefins with the complex as the catalyst was evaluated, which indicated that the complex has effective catalytic efficiency in the oxidation of several aliphatic and aromatic substrates by using tert-butyl hydrogen peroxide as oxidant.
A new clade of styrene monooxygenases for (R)-selective epoxidation
Xiao, Hu,Dong, Shuang,Liu, Yan,Pei, Xiao-Qiong,Lin, Hui,Wu, Zhong-Liu
, p. 2195 - 2201 (2021/04/12)
Styrene monooxygenases (SMOs) are excellent enzymes for the production of (S)-enantiopure epoxides, but so far, only one (R)-selective SMO has been identified with a narrow substrate spectrum. Mining the NCBI non-redundant protein sequences returned a new distinct clade of (R)-selective SMOs. Among them,SeStyA fromStreptomyces exfoliatus,AaStyA fromAmycolatopsis albispora, andPbStyA fromPseudonocardiaceaewere carefully characterized and found to convert a spectrum of styrene analogues into the corresponding (R)-epoxides with up to >99% ee. Moreover, site 46 (AaStyA numbering) was identified as a critical residue that affects the enantioselectivity of SMOs. Phenylalanine at site 46 was required for the (R)-selective SMO to endow excellent enantioselectivity. The identification of new (R)-selective SMOs would add a valuable green alternative to the synthetic tool box for the synthesis of enantiopure (R)-epoxides.
X-ray Structure-Guided Discovery of a Potent, Orally Bioavailable, Dual Human Indoleamine/Tryptophan 2,3-Dioxygenase (hIDO/hTDO) Inhibitor That Shows Activity in a Mouse Model of Parkinson’s Disease
Ning, Xiang-Li,Li, Yu-Zhi,Huo, Cui,Deng, Ji,Gao, Cheng,Zhu, Kai-Rong,Wang, Miao,Wu, Yu-Xiang,Yu, Jun-Lin,Ren, Ya-Li,Luo, Zong-Yuan,Li, Gen,Chen, Yang,Wang, Si-Yao,Peng, Cheng,Yang, Ling-Ling,Wang, Zhou-Yu,Wu, Yong,Qian, Shan,Li, Guo-Bo
supporting information, p. 8303 - 8332 (2021/06/30)
Human indoleamine 2,3-dioxygenase 1 (hIDO1) and tryptophan 2,3-dioxygenase (hTDO) have been closely linked to the pathogenesis of Parkinson’s disease (PD); nevertheless, development of dual hIDO1 and hTDO inhibitors to evaluate their potential efficacy against PD is still lacking. Here, we report biochemical, biophysical, and computational analyses revealing that 1H-indazole-4-amines inhibit both hIDO1 and hTDO by a mechanism involving direct coordination with the heme ferrous and ferric states. Crystal structure-guided optimization led to23, which manifested IC50values of 0.64 and 0.04 μM to hIDO1 and hTDO, respectively, and had good pharmacokinetic properties and brain penetration in mice.23showed efficacy against the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-induced mouse motor coordination deficits, comparable to Madopar, an anti-PD medicine. Further studies revealed that different from Madopar,23likely has specific anti-PD mechanisms involving lowering IDO1 expression, alleviating dopaminergic neurodegeneration, reducing inflammatory cytokines and quinolinic acid in mouse brain, and increasing kynurenic acid in mouse blood.