1570-45-2Relevant articles and documents
Synthesis, characterization, antioxidant activities, and DNA-binding studies of (E)-N′-[1-(pyridin-2-yl)ethylidene]isonicotinohydrazide and its Pr(III) and Nd(III) complexes
Hao, Zhong-Yan,Liu, Qi-Wan,Xu, Jun,Jia, Lei,Li, Shao-Bai
, p. 1306 - 1312 (2010)
A new ligand, (E)-N′-[1-(pyridin-2-yl)ethylidene]isonicotinohydrazide (HL), was prepared by condensation of 2-acetylpyridine and isonicotinohydrazide in ethanol. Its two lanthanide(III) complexes, [NdIII(L) 2(NO3)(CH3OH)2]?CH 3CH2OH (1), and [PrIII(L)2(NO 3)(CH3OH)2]?CH3CH 2OH (2), have been synthesized and characterized on the basis of element analyses, molar conductivities and IR spectra. The structure of complex 2 has been confirmed by X-ray diffraction. In addition, the DNA-binding properties of the two complexes have been investigated by electronic absorption spectroscopy, fluorescence spectroscopy, circular dichroic (CD) spectroscopy and viscosity measurements. The experimental results suggest that the two complexes bind to DNA via a groove binding mode, and the binding affinity of complex 2 is higher than that of complex 1. Furthermore, the antioxidant activities (superoxide and hydroxyl radical) of the ligand and its metal complexes were determined by spectrophotometry methods in vitro. These complexes were found to possess potent antioxidant activity and be superior to standard antioxidant like mannitol.
Transition metal complexes of N′-(2-(hydroxyimino)propanoyl)isonicotinohydrazide: Synthesis, characterization, DNA interaction and anticancer evaluation
Hegde, Divya,Naik, Ganesh N.,Vadavi, Ramesh S.,Shyam Kumar,Barretto, Delicia A.,Gudasi, Kalagouda B.
, p. 301 - 315 (2017)
A new tetradentate chelating ligand, N′-(2-(hydroxyimino)propanoyl)isonicotinohydrazide and its selective transition metal complexes have been synthesized and evaluated for anticancer behavior. The ligand structure was determined by single-crystal X-ray crystallography. All complexes were investigated by elemental, thermogravimetric analysis, IR, NMR, ESI Mass and electronic spectroscopic studies. The ligand exhibited monoclinic lattice structure with Cc space group, having 4 ligand molecules in each unit cell. The geometrical isomerism (E and Z) was observed in ligand due to the restricted rotation along the >C[dbnd]N– functional group. The interaction of ligand and complexes with calf-thymus DNA (CT-DNA) has been extensively studied using absorption, emission, viscosity and thermal denaturation studies with E. coli DNA. The DNA cleavage properties were screened using plasmid pBR322 DNA by gel electrophoresis method. Complexes have been evaluated for their in vitro antiproliferative activity against human cancer cells of different origin such as MCF-7, Mia-Pa-Ca-2 and DU-145 by using SRB (sulforhodamine B) assay, in which iron complex have shown better antiproliferative activity compared to remaining complexes.
Development of a Novel Chemoenzymatic Process for (S)-1-(Pyridin-4-yl)-1,3-propanediol
Chen, Shao-Xin,Peng, Peng,Tang, Jia-Wei,Wang, Hong-Yi,Yan, Hai-Jun,Zhang, Fu-Li
, p. 2890 - 2897 (2020)
We first developed a novel and efficient chemoenzymatic process to prepare (S)-1-(pyridin-4-yl)-1,3-propanediol, a vital HepDirect prodrug intermediate, from inexpensive and commercially available isonicotinic acid. Through this process, we provide a creative way to obtain the key chiral intermediate, β-hydroxyester, with ketoreductase (KRED) EA. After optimization of the process, we performed the reaction on a 100 g scale with a substrate concentration of up to 150 g/L, a yield of 93%, and an ee value of up to 99.9%. Additionally, we used a simple and effective NaBH4/MgCl2 reduction system to obtain (S)-1-(pyridin-4-yl)-1,3-propanediol with >99.9% ee and an 80% yield. This novel chemoenzymatic process has the potential to be a cost-effective and environmentally friendly process suitable for industrial use.
A facile and versatile electro-reductive system for hydrodefunctionalization under ambient conditions
Huang, Binbin,Guo, Lin,Xia, Wujiong
supporting information, p. 2095 - 2103 (2021/03/26)
A general electrochemical system for reductive hydrodefunctionalization is described, employing the inexpensive and easily available triethylamine (Et3N) as a sacrificial reductant. This protocol is characterized by facile operation, sustainable conditions, and exceptionally wide substrate scope covering the cleavage of C-halogen, N-S, N-C, O-S, O-C, C-C and C-N bonds. Notably, the selectivity and capability of reduction can be conveniently switched by simple incorporation or removal of an alcohol as a co-solvent.
Fluorovinylsulfones and -Sulfonates as Potent Covalent Reversible Inhibitors of the Trypanosomal Cysteine Protease Rhodesain: Structure-Activity Relationship, Inhibition Mechanism, Metabolism, and in Vivo Studies
Jung, Sascha,Fuchs, Natalie,Johe, Patrick,Wagner, Annika,Diehl, Erika,Yuliani, Tri,Zimmer, Collin,Barthels, Fabian,Zimmermann, Robert A.,Klein, Philipp,Waigel, Waldemar,Meyr, Jessica,Opatz, Till,Tenzer, Stefan,Distler, Ute,R?der, Hans-Joachim,Kersten, Christian,Engels, Bernd,Hellmich, Ute A.,Klein, Jochen,Schirmeister, Tanja
, p. 12322 - 12358 (2021/09/02)
Rhodesain is a major cysteine protease of Trypanosoma brucei rhodesiense, a pathogen causing Human African Trypanosomiasis, and a validated drug target. Recently, we reported the development of α-halovinylsulfones as a new class of covalent reversible cysteine protease inhibitors. Here, α-fluorovinylsulfones/-sulfonates were optimized for rhodesain based on molecular modeling approaches. 2d, the most potent and selective inhibitor in the series, shows a single-digit nanomolar affinity and high selectivity toward mammalian cathepsins B and L. Enzymatic dilution assays and MS experiments indicate that 2d is a slow-tight binder (Ki = 3 nM). Furthermore, the nonfluorinated 2d-(H) shows favorable metabolism and biodistribution by accumulation in mice brain tissue after intraperitoneal and oral administration. The highest antitrypanosomal activity was observed for inhibitors with an N-terminal 2,3-dihydrobenzo[b][1,4]dioxine group and a 4-Me-Phe residue in P2 (2e/4e) with nanomolar EC50 values (0.14/0.80 μM). The different mechanisms of reversible and irreversible inhibitors were explained using QM/MM calculations and MD simulations.
