Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium‐catalyzed highly ...enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom‐economical approach to an array of 2‐arylpropanoic acids including several commonly used non‐steroidal anti‐inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2‐arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio‐ and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate‐limiting step.
A Pd‐catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water for the synthesis of 2‐arylpropanoic acids has been developed. Several non‐steroidal anti‐inflammatory drugs including ibuprofen, naproxen, flurbiprofen, fenoprofen, and ketoprofen were synthesized in high yields and ees in gram scale.
AIM: To investigate the anti-tumor effects of equol in gastric cancer cells and the underlying molecular mechanisms.METHODS: MGC-803 cells were employed for in vitro experiments in this study. Cells ...were treated with control(vehicle,0.1% DMSO) or equol under specified dose titration or time courses. Cell viability was examined by MTS assay,and the levels of Ki67 were determined by q PCR and immunofluorescent assay. Changes in cell cycle distribution and apoptosis rate were detected by flow cytometry. The m RNA expression of cyclin E1 and P21WAF1 was determined by q PCR. The protein levels of cell cycle regulators,PARP and Caspase-3 cleavage,and the phosphorylation of Akt were examined by Western blot. In addition,to characterize the role of elevated Akt activation in the anti-tumor effect exerted by equol,Ly294002,a PI3K/AKT pathway inhibitor,was used to pretreat MGC-803 cells. RESULTS: Equol(5,10,20,40,or 80 μmol/L) inhibited viability of MGC-803 cells in a dose- and timedependent manner after treatment for 24,36,or 48 h(P < 0.05 for all). Equol also decreased the m RNA(P <0.05 for 12 and 24 h treatment) and protein levels of Ki67. Equol treatment significantly induced G0/G1 cell cycle arrest(P < 0.05),with the percentages of G0/G1 cells of 32.23% ± 3.62%,36.31% ± 0.24%,45.58% ± 2.29%,and 65.10% ± 2.04% for equol(0,10,20,or 30 μmol/L) treatment,respectively,accompanied by a significant decrease of CDK2/4(P < 0.05 for 24 and 48 h treatment) and Cyclin D1/Cyclin E1(P < 0.05),and an increased level of P21WAF1(P < 0.05). A marked increase of apoptosis was observed,with the percentages of apoptotic cells of 5.01% ± 0.91%,14.57% ± 0.99%,37.40% ± 0.58%,and 38.46% ± 2.01% for equol(0,5,10,or 20 μmol/L) treatment,respectively,accompanied by increased levels of cleaved PARP and caspase-3. In addition,we found that equol treatment increased P-Akt(Ser473 and Thr308) at 12 and 24 h compared to vehicle-treated control; longer treatment for 48 h decreased P-Akt(Ser473 and Thr308). P-Akt at Thr450,however,was decreased by equol treatment at all time points examined(P < 0.05 for all). Moreover,Akt inhibition by Ly294002 could not prevent but led to enhanced G0/G1 arrest and apoptosis. CONCLUSION: Equol inhibits MGC-803 cells proliferation by induction of G0/G1 arrest and apoptosis. Its anti-cancer effects are likely mediated by dephosphorylation of Akt at Thr450.
Three novel porphyrins, including two Schiff‐bases porphyrins, 5,10,15‐triphenyl‐20‐4‐(2‐(4‐formyl)phenoxy)ethoxyphenyl porphyrin (H2Pp(1)), ...5,10,15‐triphenyl‐20‐4‐(2‐(4‐hydroxyimino)phenoxy)ethoxyphenyl porphyrin (H2Pp(2)) and 5,10,15‐triphenyl‐20‐4‐(2‐(4‐m‐hydroxyanilinodeneformyl)phenoxy)ethoxyphenyl porphyrin (H2Pp(3)), as well as three metalloporphyrins (CuPp (1a), ZnPp (1b), and CoPp (1c)) of porphyrin H2Pp(1) were synthesized. Their molecular structures were characterized by 1H‐NMR, MS, UV/VIS, and FT‐IR spectra. Furthermore, they were evaluated by their cytotoxicities against human epidermal squamous cell carcinoma cell (A431) and normal human horn cells (HaCaT) in vitro with MTT assay. Interestingly, these porphyrins and metalloporphyrins, which had a negligible cytotoxicity to HaCaT cells, showed highly cytotoxicity against A431 cells with IC50 values in the range of 6.6–9.8 μM, and metalloporphyrins exhibited higher cytotoxicity than that of metal‐free porphyrins.
In this work, one new porphyrin, 5, 10, 15, 20-tetrakis(4-N-pyrazolyl)phenyl porphyrin (H2Pp) was synthesized and characterized. The single crystal structures of H2Pp and its cobalt(II) porphyrin ...(Co(II)Pp) were obtained with a space group of P1− and I2/c, respectively. The porphyrin macrocycle is close to a perfect plane in H2Pp, while Co(II)Pp exhibits a saddle-type distortion due to the formation of shorter Co–N coordination bonds. In H2Pp, the molecules are interconnected through π⋯π and C–H⋯π interactions to form 3D architecture, while in Co(II)Pp the porphyrin molecules are interlinked only by C–H⋯π interactions to yield 3D structure. We examined the UV–vis spectra and fluorescent spectra of H2Pp and Co(II)Pp in CH2Cl2 and solid state at room temperature. In addition, the catalytic activities of Co(II)Pp to the ethylbenzene oxidation was examined, the results indicate that Co(II)Pp exhibits a high selectivity to acetophenone (>99%) with the conversion of 83%.
In H2Pp, the molecules are interconnected through π⋯π and C–H···π interactions to form 3D structure, while in Co(II)Pp the porphyrin molecules are interlinked only by C–H⋯π interactions to yield 3D structure. Co(II)Pp displays high catalytic activity with the only product acetophenone quantitatively in 83%. Display omitted
•One new pyrazole-functionalized porphyrin and Co(II) porphyrin were synthesized and characterized structurally.•Insertion of Co(II) ion into porphyrin macrocycle leads to a saddle distortion of Co(II) porphyrin plane.•UV–vis and fluorescent spectra of the two compounds in CH2Cl2 and solid state were compared.•Co(II)Pp shows high catalytic activities to ethylbenzene oxidation with 83% conversion.
Three novel porphyrin-Schiff base conjugates derived from tetra(4-aminophenyl)porphyrin (
TAPP
), namely, tetra4-(4-hydroxy benzylideneamino)phenyl porphyrin (
3a
), tetra4-(2-thienyldeneamino)phenyl ...porphyrin (
3b
) and tetra4-(2-pyridyldeneamino)phenyl porphyrin (
3c
), were synthesized and characterized by IR, UV-vis,
1
H NMR, HRMS and elementary analysis. Their biological activities against human epidermoid carcinoma (A431) cells were evaluated with an MTT assay. As we expected, the porphyrin conjugates showed negligible cytotoxicity to A431 cells in the absence of light, while their phototoxic activities were improved after irradiated with LED lamp (425 nm) and increased significantly with increased doses. The fluorescence microscope pictures revealed that the three porphyrin-Schiff conjugates could diffuse into skin cancer cells, demonstrating that these compounds are potential candidates for photodynamic therapy agents.
Three novel porphyrin-Schiff base conjugates were synthesized and characterized. Their phototoxic activities were improved after irradiation and increased significantly with the increase of doses against A431 cells.
Asymmetric hydroxycarbonylation is one of the most fundamental yet challenging methods for the synthesis of carboxylic acids. Herein, we reported the development of a palladium‐catalyzed highly ...enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water. A monodentate phosphoramidite ligand L6 plays vital role in the reaction. The reaction tolerates a range of functional groups, and provides a facile and atom‐economical approach to an array of 2‐arylpropanoic acids including several commonly used non‐steroidal anti‐inflammatory drugs. The catalytic system has also enabled an asymmetric Markovnikov hydroalkoxycarbonylation of vinyl arenes with alcohols to afford 2‐arylpropanates. Mechanistic investigations suggested that the hydropalladation is irreversible and is the regio‐ and enantiodetermining step, while hydrolysis/alcoholysis is probably the rate‐limiting step.
A Pd‐catalyzed highly enantioselective Markovnikov hydroxycarbonylation of vinyl arenes with CO and water for the synthesis of 2‐arylpropanoic acids has been developed. Several non‐steroidal anti‐inflammatory drugs including ibuprofen, naproxen, flurbiprofen, fenoprofen, and ketoprofen were synthesized in high yields and ees in gram scale.
The socio-economic burden of acute exacerbation of chronic obstructive pulmonary disease (AECOPD) in Beijing is not fully understood. The study investigated the hospitalization cost in patients with ...AECOPD and the associated factors.
A multi-center, retrospective study was conducted in the four hospitals in Beijing including two level III hospitals and two level II hospitals. Patients with AECOPD admitted to the hospitals between January and December in 2006 were enrolled. The hospitalization cost and its relationship with disease severity and treatment were analyzed.
Totally 439 patients were enrolled with 294 men (67.0%) and a mean age 73.4 years. The mean hospital stay was 20.7 days. A total of 204 patients (46.5%) had respiratory failure, 153 (34.9%) with cor pulmonale, 123 (28.0%) with coronary artery disease, 231 (52.6%) with hypertension, 70 (15.9%) with cerebrovascular disease and 32 (7.3%) with renal failure. The percentage of drug cost to total cost was the highest (71.2%), followed by laboratory cost (16.7%), therapy cost (9.7%), oxygen cost (7.3%), radiology cost (4.5%), examination cost (4.5%), bed cost (4.1%). Correlation analysis showed that cost was positively correlated with age, hospitalization days, co-morbidities such as respiratory failure and cor pulmonale, hypertension. Three hundred and twenty-one patients were further analyzed. The hospitalization cost increased in patients with non-invasive ventilation (P < 0.01), invasive mechanical ventilation (P < 0.01), ICU stay (P < 0.01), antibiotics (P < 0.05), systemic steroids (P < 0.01), and poor prognosis (P < 0.05). Correlation analysis showed that the hospitalization cost was negatively correlated with percentage forced expiratory volume in 1 second (FEV(1)%) (r = -0.149, P < 0.05), pH (r = -0.258, P < 0.01), and PaO(2) (r = -0.131, P < 0.05), positively correlated with PaCO2 (r = 0.319, P < 0.01), non-invasive positive pressure ventilation (r = 0.375, P < 0.01) and duration (r = 0.463, P < 0.01), invasive mechanical ventilation (r = 0.416, P < 0.01) and duration (r = 0.511, P < 0.01), ICU stay (r = 0.390, P < 0.01) and duration (r = 0.650, P < 0.01), antibiotics (r = 0.140, P < 0.05) and systemic steroids (r = 0.202, P < 0.01).
AECOPD had a great impact on healthcare resources utilization. Disease severity, use of non-invasive or invasive ventilation, ICU stay and usage of antibiotics and systemic steroids were the major determinants of hospitalization cost. Long-term regular treatment aimed at reducing the frequency of acute exacerbation will lower the social and economic burden of chronic obstructive pulmonary disease (COPD).
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