2459-09-8Relevant articles and documents
Comparative Studies of 2-, 3-, and 4-Pyridylpalladium(II) Complexes: Synthesis and Properties
Isobe, Kiyoshi,Nakamura, Yukio,Miwa, Toshio,Kawaguchi, Shinichi
, p. 149 - 158 (1987)
Oxidative addition reactions of bromopyridines to tetrakis(triphenylphosphine)palladium(0) gave (1b), trans- (2b), and trans- (3b), which were converted on treatment with triethylphosphine to trans- complexes (1d, 2d, 3d, respectively).Titration with perchloric acid in dioxane-water (1:1 by volume) indicated the basicity sequence of these complexes: 2-pyridyl>>4-pyridyl>3-pyridyl.The bromide ligand in 1b-3b can readily be replaced by Cl-, I-, N3-, NCO-,and NCS-.In each corresponding series the relative thermal stability is in the sequence of 2-pyridyl>4-pyridyl>3-pyridyl.The pyridyl complexes containing triphenylphosphine react with carbon monoxide at ambient temperature and pressure to afford acyl complexes, which produce the corresponding esters by reactions with methanol.They also act as catalysts for cross coupling reactions of bromopyridines.
Hierarchical self-assembly of surfactant-encapsulated and organically grafted polyoxometalate complexes
Wang, Huanbing,Yan, Yi,Li, Bao,Bi, Lihua,Wu, Lixin
, p. 4273 - 4282 (2011)
A series of surfactant-encapsulated and organically grafted polyoxometalates (SEOPs) were prepared through a co-precipitation procedure. Through a rational selection of the molecular components in the structure of the complex, SEOP complexes self-assemble into ordered aggregates with two different hierarchical self-assembled structures in an organic solvent mixture of dichloromethane and methanol in different volume ratios. FTIR, 1H NMR, and X-ray photoelectron spectroscopy were used to characterize the self-assembly process and the involved driving forces. In a weakly polar solvent, SEOPs aggregated into fibers with a lamellar structure. When the solvent polarity was increased, SEOPs formed ribbonlike aggregates with a tetragonal structure. The change of the hierarchical self-assembled structure was deduced in regard to the arrangement of alkyl chains, electrostatic interactions, and hydrogen bonding between the pyridyl groups and terminal oxygen atoms of the polyoxometalates. The ribbonlike aggregates exhibit birefringence due to the ordered arrangement of SEOPs in the microstructure. Copyright
Thermodynamic properties of three pyridine carboxylic acid methyl ester isomers
Ribeiro Da Silva, Maria D. M. C.,Freitas, Vera L. S.,Santos, Luis M. N. B. F.,Fulem, Michal,Sottomayor,Monte, Manuel J. S.,Acree Jr.
, p. 580 - 585 (2007)
The present work reports the values of the standard (po = 0.1 MPa) molar energies of combustion for the liquid isomers methyl picolinate and methyl isonicotinate and for the crystalline isomer methyl nicotinate measured by static bomb calorimetry. The molar enthalpies of vaporization of the three isomers at T = 298.15 K as well as the molar enthalpies of sublimation of two of them (methyl picolinate and methyl nicotinate) were derived from vapor pressure measurements at different temperatures using a static method. The molar enthalpies of vaporization at T = 298.15 K of methyl picolinate and methyl isonicotinate were also measured using Calvet microcalorimetry. The thermal behavior of the compounds was studied by differential scanning calorimetry, and the temperatures and the molar enthalpies of fusion were determined using this technique. The experimental results were used to derive the gaseous standard molar enthalpies of formation, at 298.15 K, of the three pyridinecarboxylic acid methyl ester isomers and the triple points of the ortho and meta isomers.
Arene-ruthenium(II) complexes containing 5-fluorouracil-1-methyl isonicotinate: Synthesis and characterization of their anticancer activity
Liu, Kuan-Guan,Cai, Xiao-Qing,Li, Xian-Chuan,Qin, Da-An,Hu, Mao-Lin
, p. 78 - 83 (2012)
To integrate the respective advantages exhibited by half-sandwich arene-Ru(II) fragments and 5-FU derivatives, a multifunctional ligand that links isonicotinic acid and 5-Fu (5-fluorouracil) through an ester bond for achieving the enhanced effect and an organoruthenium(II) complex containing this ligand were prepared and characterized by standard analytical techniques. The cytotoxicity of these organoruthenium(II) compounds containing 5-fluorouracil-1-methyl isonicotinate against BEL-7402 human cancer cells was moderately improved, which implies synergistic action of 5-Fu and the half-sandwich-structured arene-Ru(II). In addition, the organoruthenium(II) compounds containing isonicotinic acid and methyl isonicotinate are also discussed, and the crystal structure of [(η6-p-cymene)RuCl 2(methyl isonicotinate)] (4) was determined; its piano-stool structure is analyzed in this paper.
Silver-coordination polymer network combining antibacterial action and shape memory capabilities
Wang, Lin,Wang, Wenxi,Di, Shubin,Yang, Xifeng,Chen, Hongmei,Gong, Tao,Zhou, Shaobing
, p. 32276 - 32282 (2014)
In this study, a multifunctional polymer network is achieved by first synthesizing an isonicotinate-functionalized polyester (PIE) via classical melt-condensation polymerization, and secondly, the pendant of the pyrazinamide groups on the polyester side chains is coordinated with Ag ions to form a physically cross-linked network. Thermo property analysis and dynamic mechanical analysis reveal that the Ag-coordination polymer network possesses an excellent thermo-induced shape memory function, both under air and physiological conditions, due to a wide glass transition temperature region. The Ag ion concentration coordinated with the polymer was optimized to achieve the best shape memory effect using atomic absorption spectrometry. Moreover, the coordinated polyester can act as a reservoir of bactericidal Ag ions, in which the Ag ions are released and measured with inductively coupled plasma mass spectrometry, and in turn the antibacterial function is realized. Finally, the result of an Alamar blue assay reveals that the Ag-coordinated polyester has good cytocompatibility despite the introduction of a certain amount of Ag ions. Therefore, the multifunctional polymer has great potential applications in the biomedical field, e.g., burn wound dressings. the Partner Organisations 2014.
GPR52 Antagonist Reduces Huntingtin Levels and Ameliorates Huntington's Disease-Related Phenotypes
Wang, Congcong,Zhang, Yu-Fang,Guo, Shimeng,Zhao, Quan,Zeng, Yanping,Xie, Zhicheng,Xie, Xin,Lu, Boxun,Hu, Youhong
, p. 941 - 957 (2020/11/30)
GPR52 is an orphan G protein-coupled receptor (GPCR) that has been recently implicated as a potential drug target of Huntington's disease (HD), an incurable monogenic neurodegenerative disorder. In this research, we found that striatal knockdown of GPR52 reduces mHTT levels in adult HdhQ140 mice, validating GPR52 as an HD target. In addition, we discovered a highly potent and specific GPR52 antagonist Comp-43 with an IC50 value of 0.63 μM by a structure-activity relationship (SAR) study. Further studies showed that Comp-43 reduces mHTT levels by targeting GPR52 and promotes survival of mouse primary striatal neurons. Moreover, in vivo study showed that Comp-43 not only reduces mHTT levels but also rescues HD-related phenotypes in HdhQ140 mice. Taken together, our study confirms that inhibition of GPR52 is a promising strategy for HD therapy, and the GPR52 antagonist Comp-43 might serve as a lead compound for further investigation.
Design, synthesis, antibacterial evaluation, and computational studies of hybrid oxothiazolidin–1,2,4-triazole scaffolds
Pathak, Prateek,Novak, Jurica,Shukla, Parjanya K.,Grishina, Maria,Potemkin, Vladimir,Verma, Amita
, (2021/03/08)
Bacterial infections are a serious threat to human health due to the development of resistance against the presently used antibiotics. The problem of growing and widespread antibiotic resistance is only getting worse with the shortage of new classes of antibiotics, creating a substantial unmet medical need in the treatment of serious bacterial infections. Therefore, in the present work, we report 18 novel hybrid thiazolidine–1,2,4-triazole derivatives as DNA gyrase inhibitors. The derivatives were synthesized by multistep organic synthesis and characterized by spectroscopic methods (1H and 13C nuclear magnetic resonance and mass spectroscopy). The derivatives were tested for DNA gyrase inhibition, and the result emphasized that the synthesized derivatives have a tendency to inhibit the function of DNA gyrase. Furthermore, the compounds were also tested for antibacterial activity against three Gram-positive (Bacillus subtilis [NCIM 2063], Bacillus cereus [NCIM 2156], Staphylococcus aureus [NCIM 2079]) and two Gram-negative (Escherichia coli [NCIM 2065], Proteus vulgaris [NCIM 2027]) bacteria. The derivatives showed a significant-to-moderate antibacterial activity with noticeable antibiofilm efficacy. Quantitative structure–activity relationship (QSAR), ADME (absorption, distribution, metabolism, elimination) calculation, molecular docking, radial distribution function, and 2D fingerprinting were also performed to elucidate fundamental structural fragments essential for their bioactivity. These studies suggest that the derivatives 10b and 10n have lead antibacterial properties with significant DNA gyrase inhibitory efficacy, and they can serve as a starting scaffold for the further development of new broad-spectrum antibacterial agents.
N-acylhydrazones confer inhibitory efficacy against New Delhi metallo-β-lactamase-1
Gao, Han,Li, Jia-Qi,Kang, Peng-Wei,Chigan, Jia-Zhu,Wang, Huan,Liu, Lu,Xu, Yin-Sui,Zhai, Le,Yang, Ke-Wu
, (2021/07/07)
The expression of β-lactamases, especially metallo-β-lactamases (MβLs) in bacteria is one of the main causes of drug resistance. In this work, an effective N-acylhydrazone scaffold as MβL inhibitor was constructed and characterized. The biological activity assays indicated that the synthesized N-acylhydrazones 1–11 preferentially inhibited MβL NDM-1, and 1 was found to be the most effective inhibitor with an IC50 of 1.2 μM. Analysis of IC50 data revealed a structure–activity relationship, which is that the pyridine and hydroxylbenzene substituents at 2-position improved inhibition of the compounds on NDM-1. ITC and enzyme kinetics assays suggested that it reversibly and competitively inhibited NDM-1 (Ki = 0.29 ± 0.05 μM). The synthesized N-acylhydrazones showed synergistic antibacterial activities with meropenem, reduced 4–16-fold MIC of meropenem on NDM-1- producing E. coli BL21 (DE3), while 1 restored 4-fold activity of meropenem on K. pneumonia expressing NDM-1 (NDM-K. pneumoniae). The mice experiments suggested that 1 combined meropenem to fight against NDM-K. pneumoniae infection in the spleen and liver. Cytotoxicity assays showed that 1 and 2 have low cytotoxicity. This study offered a new framework for the development of NDM-1 inhibitors.
1,2,4-Triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds: A potent ameliorant of carrageenan-induced inflammation by lessening proinflammatory mediators
Pathak, Prateek,Shukla, Parjanya K.,Naumovich, Vladislav,Grishina, Maria,Verma, Amita,Potemkin, Vladimir
, (2019/11/16)
Inflammation acts as an alarming signal for the progression of various biological complications. Various reports in the literature have revealed that heterocycle-containing synthetic compounds have a restorative capability against acute and chronic inflammatory stages. In the current study, we synthesized a series of 1,2,4-triazole-conjugated 1,3,4-thiadiazole hybrid scaffolds and evaluated their impacts against carrageenan-induced paw edema and proinflammatory markers in Wistar rats. Further, 3D QSAR study (three-dimensional quantitative structure–activity relationships), ADMET (absorption, distribution, metabolism, and excretion) profiling, and docking studies were performed to determine the possible mechanism of the action of the derivatives. The study shows that the most active derivatives, 13f and 13g, have optimal logP, a higher anti-inflammatory activity score, and poor metabolism at various sites of cytochrome P450. The docking studies recommended that the synthesized compounds have a similar affinity as the ligands A307, 63X, and S58 to interact with tumor necrosis factor-α, COX-1, and COX-2. So, these molecules will definitely hold a promise for the future drug development initiative.
Design, synthesis, and biological evaluation of new challenging thalidomide analogs as potential anticancer immunomodulatory agents
El-Zahabi, Mohamed Ayman,Sakr, Helmy,El-Adl, Khaled.,Zayed, Mohamed,Abdelraheem, Adel S.,Eissa, Sally I.,Elkady, Hazem,Eissa, Ibrahim H.
, (2020/09/16)
Thalidomide and its analogs are immunomodulatory drugs that inhibit the production of certain inflammatory mediators associated with cancer. In the present work, a new series of thalidomide analogs was designed and synthesized to obtain new effective antitumor immunomodulatory agents. The synthesized compounds were evaluated for their cytotoxic activities against a panel of four cancer cell lines (HepG-2, HCT-116, PC3 and MCF-7). Compounds 33h, 33i, 42f and 42h showed strong potencies against all tested cell lines with IC50 values ranging from 14.63 to 49.90 μM comparable to that of thalidomide (IC50 values ranging from 32.12 to 76.91 μM). The most active compounds were further evaluated for their in vitro immunomodulatory activities via estimation of human tumor necrosis factor alpha (TNF-α), human caspase-8 (CASP8), human vascular endothelial growth factor (VEGF), and nuclear factor kappa-B P65 (NF-κB P65) in HCT-116 cells. Thalidomide was used as a positive control. Compounds 33h and 42f showed a significant reduction in TNF-α. Furthermore, compounds 33i and 42f exhibited significant elevation in CASP8 levels. Compounds 33i and 42f inhibited VEGF. In addition, compound 42f showed significant decrease in levels of NF-κB p65. Moreover, apoptosis and cell cycle tests of the most active compound 42f, were performed. The results indicated that compound 42f significantly induce apoptosis in HCT-116 cells and arrest cell cycle at the G2/M phase.
