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1.
Durairaj Gopalakrishnan Santhanam Srinath Baburaj Baskar Nattamai S.P. Bhuvanesh Mani Ganeshpandian 《应用有机金属化学》2019,33(3)
Two organometallic Ru(II)‐p‐cymene complexes of the type [Ru(ηp>6 p>‐p‐cymene)(L)Cl]PF6 1 and 2 , where L is N,N‐bis(4‐isopropylbenzylidene)ethane‐1,2‐diamine (bien, L1 ) or N,N‐bis (pyren‐2‐ylmethylene)ethane‐1,2‐diamine (bpen, L2 ) have been prepared and characterized well. Because of appended pyrenyl groups in coordinated bpen ligand, the complex 2 exhibits higher DNA and protein binding than complex 1 in which isopropylbenzyl groups are incorporated. Interestingly, the luminescent characteristic complex 2 is unique in displaying DNA cleavage after light activation by UVA light at 365 nm through oxygen dependent mechanism. AFM analysis attests the photo‐induced DNA fragmentation ability of complex 2 . Also, the complex 2 cleaves the protein after light exposure in a non‐specific manner suggesting that it can act as a protein photo cleaving agent. In contrast to the trend of DNA and protein interaction of complexes, the complex 1 exhibits cytotoxic activity against human breast carcinoma ( MCF‐7 ) and liver carcinoma ( HepG2 ) with potency higher than that of complex 2 due to enhanced hydrophobicity of isopropyl groups present in p‐cymene and bien ligands. Indeed, complex 2 is inactive against MCF‐7 and HepG2 cancer cell lines even up to 200 μM concentration. The AO/EB staining assay reveals that the complex 1 is able to induce late apoptotic mode of cell death in breast cancer cells, which is further confirmed by inter‐nucleosomal DNA cleavage. Furthermore, the complexes 1 and 2 are evaluated for their catalytic activities and found to be working well for the β‐carboline directed C–H arylation to afford the desired products in good yield (40–47%). 相似文献
2.
The p‐arsanilic acid (p‐ASA), as an aromatic organoarsenic compounds, had received considerable concerns for their potential toxicity and carcinogenic properties. It was essential to detect p‐ASA with a facile method. In this paper, an europium based fluorescent metal–organic framework (MOF) [Eu2(clhex)·2H2O)]·H2O ( BUC‐69 ) was successfully prepared under hydrothermal conditions with 1,2,3,4,5,6‐cyclohexanehexacarboxylic acid (H6clhex) as organic linker. BUC‐69 displayed superior fluorescence capability to achieve selective and sensitive detection toward p‐ASA in water, which presented the first example of a MOF‐based sensor to detect p‐ASA. BUC‐69 showed excellent chemical stability in solutions under pH ranging from 4 to 12, which makes it be a potential sensor both in acidity and alkalinity condition. Significantly, BUC‐69 performed well in fluorescent sensing of p‐ASA at a low concentration (10p>?6 p> M) in the simulated wastewater prepared with real lake water, and the results were comparable to the values detected by Inductively Coupled Plasma Optical Emission Spectrometer (ICP‐OES). The corresponding mechanism of fluorescent sensing toward p‐ASA with BUC‐69 was proposed and affirmed. 相似文献
3.
Mycophenolic acid (MPA), a frequently used immunosuppressant, exhibits large inter‐patient pharmacokinetic variability. This study (a) developed and validated a sensitive liquid chromatography–tandem mass spectrometry (LC–MS/MS) assay for MPA and metabolites [MPA glucuronide (MPAG) and acyl‐glucuronide (AcMPAG)] in the culture medium of HepaRG cells; and (b) characterized the metabolism interaction between MPA and p‐cresol (a common uremic toxin) in this in vitro model as a potential mechanism of pharmacokinetic variability. Chromatographic separation was achieved with a C18 column (4.6 × 250 mm,5 μm) using a gradient elution with water and methanol (with 0.1% formic acid and 2 mm ammonium acetate). A dual ion source ionization mode with positive multiple reaction monitoring was utilized. Multiple reaction monitoring mass transitions (m/z) were: MPA (320.95 → 207.05), MPAG (514.10 → 303.20) and AcMPAG (514.10 → 207.05). MPA‐d3 (323.95 → 210.15) and MPAG‐d3 (517.00 → 306.10) were utilized as internal standards. The calibration curves were linear from 0.00467 to 3.2 μg/mL for MPA/MPAG and from 0.00467 to 0.1 μg/mL for AcMPAG. The assay was validated based on industry standards. p‐Cresol inhibited MPA glucuronidation (IC50 ≈ 55 μm ) and increased MPA concentration (up to >2‐fold) at physiologically relevant substrate‐inhibitor concentrations (n = 3). Our findings suggested that fluctuations in p‐cresol concentrations might be in part responsible for the large pharmacokinetic variability observed for MPA in the clinic. 相似文献
4.
N. S. Papageorgiou 《复变函数与椭圆型方程》2019,64(1):8-25
We consider Dirichlet boundary value problems for equations involving the (p(z), q(z))-Laplacian operator in the principal part and prove the existence of one and three nontrivial weak solutions, respectively. Here, the nonlinearity in the reaction term is allowed to depend on the solution, but does not satisfy the Ambrosetti–Rabinowitz condition. The hypotheses on the reaction term ensure that the Euler–Lagrange functional, associated to the problem, satisfies both the pan class="NLM_disp-formula-image inline-formula">pt>pe":"image","src":"/na101/home/literatum/publisher/tandf/journals/content/gcov20/2019/gcov20.v064.i01/17476933.2017.1409743/20181207/images/gcov_a_1409743_ilm0001.gif"} /> pt>p;quot;type" : "image", "src" : "/na101/home/literatum/publisher/tandf/journals/content/gcov20/2019/gcov20.v064.i01/17476933.2017.1409743/20181207/images/gcov_a_1409743_ilm0001.gif"}" />pan class="no-mml-formula">pan>pan>-condition and a mountain pass geometry. 相似文献
5.
The generalized aerodynamic force (GAF) matrix is derived for the Unsteady Vortex Lattice Method (UVLM) without the assumption of out-of-plane dynamics. As a result, the approach naturally includes in-plane motion and forces unlike the doublet lattice method (DLM). The derived UVLM GAF is therefore applicable to industry-standard techniques for aeroelastic stability analyses, such as the p–k method. In this work, the fluid–structure interpolation is performed with radial basis functions for surface interpolation. The generalized aerodynamic forces computed with the UVLM are verified against the DLM from NASTRAN on a simple flat plate configuration. The ability of the UVLM to include steady loads is verified with a T-tail flutter case and the results confirm the importance of including steady loads for T-tail flutter analysis. The modal frequency domain VLM therefore provides the same level of efficiency and accuracy than the DLM, but without the restrictions and with the ability to handle complex geometries. It is therefore a viable replacement to the DLM. 相似文献
6.
Dr. Jeanette E. Stok Dr. Sharon Chow Dr. Elizabeth H. Krenske Clementina Farfan Soto Csongor Matyas Prof. Raymond A. Poirier Prof. Craig M. Williams Prof. James J. De Voss 《Chemistry (Weinheim an der Bergstrasse, Germany)》2016,22(13):4408-4412
The cytochromes P450 are hemoproteins that catalyze a range of oxidative C?H functionalization reactions, including aliphatic and aromatic hydroxylation. These transformations are important in a range of biological contexts, including biosynthesis and xenobiotic biodegradation. Much work has been carried out on the mechanism of aliphatic hydroxylation, implicating hydrogen atom abstraction, but aromatic hydroxylation is postulated to proceed differently. One mechanism invokes as the key intermediate an arene oxide (and/or its oxepin tautomer). Conclusive isolation of this intermediate has remained elusive and, currently, direct formation of phenols from a Meisenheimer intermediate is believed to be favored. We report here the identification of a P450 [P450cam (CYP101A1) and P450cin (CYP176A1)]‐generated arene oxide as a product of in vitro oxidation of tert‐butylbenzene. Computations (CBS‐QB3) predict that the arene oxide and oxepin have similar stabilities to other arene oxides/oxepins implicated (but not detected) in P450‐mediated transformations, suggesting that arene oxides can be unstable terminal products of P450‐catalyzed aromatic oxidation that can explain the origin of some observed metabolites. 相似文献
7.
Detection of p53 Gene by Using Genomagnetic Assay Combined with Carbon Nanotube Modified Disposable Sensor Technology 下载免费PDF全文
Electrochemical monitoring of DNA hybridization related to p53 gene sequence was investigated using genomagnetic assay combined with single walled carbon nanotube (SWCNT) modified pencil graphite electrodes (PGEs). The hybridization was performed either at magnetic beads (MB) surface or in solution. The enhanced guanine signal was obtained using SWCNT‐PGEs compared to one obtained by unmodified PGEs. The selectivity of genomagnetic assay was tested under optimum conditions. The DLs were calculated as 0.88 µM and 0.11 µM for hybridization performed at MB surface and solution, respectively. This selective, practical and cost effective genomagnetic assay combined with SWCNT‐PGEs is reported herein for the first time. 相似文献
8.
Cholesterol Hydroperoxides as Substrates for Cholesterol‐Metabolizing Cytochrome P450 Enzymes and Alternative Sources of 25‐Hydroxycholesterol and other Oxysterols 下载免费PDF全文
Prof. Dr. Ir. Johan E. van Lier Dr. Natalia Mast Prof. Dr. Irina A. Pikuleva 《Angewandte Chemie (International ed. in English)》2015,54(38):11138-11142
The interaction of the primary autoxidation products of cholesterol, namely 25‐ and 20ξ‐hydroperoxides, with the four principal cholesterol‐metabolizing cytochrome P450 enzymes is reported. Addition of cholesterol 25‐hydroperoxide to the enzymes CYP27A1 and CYP11A1 induced well‐defined spectral changes while generating 25‐hydroxycholesterol as the major product. The 20ξ‐hydroperoxides induced spectral shifts in CYP27A1 and CYP11A1 but glycol metabolites were detected only with CYP11A1. CYP7A1 and CYP46A1 failed to give metabolites with any of the hydroperoxides. A P450 hydroperoxide‐shunt reaction is proposed, where the hydroperoxides serve as both donor for reduced oxygen and substrate. CYP27A1 was shown to mediate the reduction of cholesterol 25‐hydroperoxide to 25‐hydroxycholesterol, a role of potential significance for cholesterol‐rich tissues with high oxidative stress. CYP27A1 may participate in the removal of harmful autoxidation products in these tissues, while providing a complementary source of 25‐hydroxycholesterol, a modulator of immune cell function and mediator of viral cell entry. 相似文献
9.
Water is essential for the proper folding of proteins and the assembly of protein–protein/ligand complexes. How water regulates complex formation depends on the chemical and topological details of the interface. The dynamics of water in the interdomain region between an E3 ubiquitin ligase (MDM2) and three different peptides derived from the tumor suppressor protein p53 are studied using molecular dynamics. The peptides show bimodal distributions of interdomain water densities across a range of distances. The addition of a hydrocarbon chain to rigidify the peptides (in a process known as stapling) results in an increase in average hydrophobicity of the peptide–protein interface. Additionally, the hydrophobic staple shields a network of water molecules, kinetically stabilizing a water chain hydrogen‐bonded between the peptide and MDM2. These properties could result in a decrease in the energy barrier associated with dehydrating the peptide–protein interface, thereby regulating the kinetics of peptide binding. © 2015 Wiley Periodicals, Inc. 相似文献
10.
Chang-Seob Seo Tae-Won Kim Young-Jung Kim So-Ra Park Hyekyung Ha Hyeun-Kyoo Shin 《Natural product research》2015,29(6):554-557
The aim of this study was to explore the protective effects of Trichosanthes kirilowii ethanol extract (TKE) against cisplatin-induced acute renal failure (ARF). In the in vitro study, TKE-pretreated porcine kidney cells (PK15) exhibited enhanced cell viability after cisplatin (15 μg mLp>? 1 p>) treatment in both MTT and crystal violet assays. PK15 cells pretreated with TKE (50 μg mLp>? 1 p>) exhibited increased glutathione content, decreased reactive oxygen species production and ameliorated p53 expression. In vivo study, rats were administered with TKE for 4 weeks before cisplatin (5 mg kgp>? 1 p>) injection. TKE (100 mg kgp>? 1 p>) decreased blood urea nitrogen and creatinine levels by 24% and 47%, respectively, in comparison with cisplatin-alone group. In addition, TKE pretreatment ameliorated cisplatin-induced oxidative stress, as evidenced by increased antioxidative enzyme levels and decreased lipid peroxidation levels. Moreover, TKE pretreatment reduced histopathological alterations in the kidney with decreased apoptotic cells. Taken together, TKE might be beneficial in treating cisplatin-induced ARF. 相似文献