Design and synthesis of 2-alkylbenzimidazole derivatives as novel non-peptide angiotensin Ⅱ AT1 receptor antagonists

A series of 2-alkylbenzimidazole derivatives 9a-n have been designed and synthesized as a novel class of non-peptide angiotensin Ⅱ AT1 receptor antagonists. The synthesized compounds were evaluated for their antagonism of angiotensin Ⅱ, induced contraction in the rabbit thoracic aortic ring and the results showed that compounds 9a, 9g and 9j exhibited potent antagonistic activity of AT1 receptor.     

Sulfation of hesperetin,naringenin and apigenin by the human cytosolic sulfotransferases: a comprehensive analysis

Abstract

Previous studies have revealed sulfation as a major pathway for the metabolism of hesperetin, naringenin and apigenin. The current study was designed to identify the human cytosolic sulfotransferase (SULT) enzyme(s) capable of sulfating these flavonoid compounds. Of the thirteen human SULTs, six (1A1, 1A2, 1A3, 1B2, 1C4, 1E1) displayed significant sulfating activity toward hesperetin, five (1A1, 1A2, 1A3, 1B2, 1C4) displayed sulfating activity towards naringenin, and four (1A1, 1A2, 1A3, 1C4) showed sulfating activity towards apigenin. Of the four human organ specimens tested, liver and intestine cytosols displayed much higher hesperetin-, naringenin- and apigenin-sulfating activity than lung and kidney cytosols. Moreover, sulfation of hesperetin, naringenin and apigenin was shown to take place in HepG2 human hepatoma cells and Caco-2 human colon adenocarcinoma cells under cultured conditions. Taken together, these results provided a biochemical basis underlying the metabolism of hesperetin, naringenin and apigenin through sulfation in humans.

     

A racemization test in peptide synthesis using 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methylmorpholinium chloride (DMT-MM)

Racemization of the C-terminal amino acid (Ala) has been studied in various solvents during coupling between 4-methoxybenzyloxycarbonyl (Z(OMe))-Gly-L-Ala-OH and phenylalanine benzyl ester (H-Phe-OBzl) with 4-(4,6-dimethoxy-1,3,5-thiazin-2-yl)-4-methylmorpholinium chloride (DMT-MM). The reaction occurred without substantial racemization in AcOEt, tetrahydrofuran (THF), N,N-dimethylformamide (DMF), CH3CN, and 2-PrOH, while a slight racemization was observed in dimethyl sulfoxide (DMSO), EtOH, and MeOH. The extent of racemization may correlate with the polarity of the solvents.     

Mononuclear nonheme ferric-peroxo complex in aldehyde deformylation

A mononuclear nonheme ferric-peroxo complex bearing a macrocyclic tetradentate N4 ligand, [(TMC)Fe(III)-O2]+, was prepared and used in mechanistic studies of aldehyde deformylation; a catalytic aldehyde deformylation by a nonheme iron(II) complex, [Fe(II)(TMC)]2+, and molecular oxygen is reported as well.     

混合配体、希土三元配合物的研究 Ⅳ.3,5—二硝基水扬酸(H_2DNSA)、邻菲咯啉(phen)、希土(RE)三元固体配合物的合成及性质

本文报道了十种希土元素与3,5-二硝基水扬酸、邻菲咯啉三元配合物的制备方法。通过元素和化学分析测定了化合物的化学组成,并用红外光谱、紫外光谱、差热分析、磁化率、X射线粉天衍射等对所合成的化合物进行了结构和性质的研究。     

Differential effects of Fas cross-linking on phospholipase D activation and related lipid metabolism in Fas-resistant A20 cells

A20 murine lymphoma cells undergoing Fas-mediated apoptosis showed increase in the activity of phospholipase D (PLD), which is involved in proliferative or mitogenic cellular responses. Using A20 cell lines that were resistant to Fas-induced apoptosis, we investigated the differential effects of Fas cross-linking on PLD activity and sphingolipid metabolism. The basal PLD activities in all of the selected three Fas-resistant clones (#5, #8, and #11) were about 2~4 folds higher than that of wild type A20 cells. Among the PLD isoforms, PLD2 expression was increased in all of the selected Fas-resistant clones. The Fas downstream signaling events triggered by Fas cross-linking, including the activations of PLD, phosphatidylcholine-specific phospholipase C (PC-PLC), sphingomyelinase (SMase), the increase in diacylglycerol (DAG) and protein phosphorylation levels, and the translocation of protein kinase C to membrane were not changed in both of Fas-resistant clone #5 and #8. In contrast, Fas cross-linking stimulated the activity of PLD, PC-PLC, and SMase, translocation of PKC, and protein phosphorylation in Fas-resistant clone #11, similar to that of wild type cells. We also found that clone #11 had a different Fas sequence encoding Fas B which has been known to inhibit Fas-induced apoptosis. These findings suggest that increased PLD2 expression resulting in increased basal PLD activity and the blockade of Fas downstream signaling cascades may be involved to limit apoptosis induced by Fas cross-linking.     

Stereoselective synthesis of (+)-SCH 351448: a unique ligand system for sodium, calcium, and other cations

(+)-SCH 351448 (Na+ salt A) was synthesized employing ring-closing olefin metathesis reaction of an open diene diester intermediate for construction of the 28-membered macrodiolide structure. The open diene diester was prepared from the monomeric hydroxy carboxylic acid and two different olefin fragments. The monomeric hydroxy acid was synthesized via Julia-Julia coupling reaction of intermediates derived from the same olefinic fragments. Oxane units in these fragments were prepared by radical cyclization reactions of beta-alkoxyacrylates. Analogous SCH 351448 salts incorporating other mono- and divalent cations may be prepared. Under acidic conditions, SCH 351448 (Na+ salt A) was the most stable complex, but SCH 351448 (Ca2+ salt) and (Na+ salt B) appear to be physiologically important species.     

Mesocellular polymer foams with unprecedented uniform large mesopores and high surface areas

Mesocellular polymer foams with uniform approximately 17 nm cellular pores were fabricated using mesocellular silica foams as inorganic templates. The mesocellular polymer foams have high surface areas up to approximately 600 m(2)g(-1) and pore volumes of 1.6 cm(3)g(-1).     

Roles of TNF-alpha and IgE in the late phase of contact hypersensitivity induced by trimellitic anhydride

Trimellitic anhydride (TMA) is widely used industrially to make epoxy and alkyd resins, plasticizers and surfactants. The purpose of this study was to investigate whether contact hypersensitivity (CHS) is induced by repeated TMA challenge and the role of TNF-alpha and IgE in the TMA-induced CHS. The repetition of the challenge enlarged the extent of an early and a late phase of CHS in TNF-alpha+/+ (B6129SF2/J) and Balb/c mice. In the late phase of TMA-induced CHS, the peak of ear swelling responses by single challenge showed at 24 h after challenge, but the peak was observed at 8 h after repeated challenge. In the TNF-alpha knockout TNF-alpha-/- (B6;129S-Tnftm1Gk1) mice, the repetition of the TMA challenges enlarged the extent of the late phase of CHS, but less than those in TNF-alpha+/+ mice. Injection of anti-TNF-alpha antibody into the peritoneal cavity of Balb/c mice significantly decreased the extent of the late phase of CHS. Subcutaneous injection of anti-IgE antibody into Balb/c mice also decreased the extent of the late phase of CHS in dose-dependent manner. Histologically, infiltration of polymorphonuclear leukocytes and eosinophils was more pronounced in repeatedly TMA-challenged TNF-alpha+/+ and Balb/c mice than in the TNF-alpha-/- mice and anti-TNF-alpha or anti-IgE antibodies treated Balb/c mice. These results indicate that mice sensitized by TMA could possibly offer a useful model to study the mechanism of CHS, and TNF-alpha and IgE may act as potential modulators in the late phase of TMA-induced CHS. Neutralization of TNF-alpha and IgE by anti-TNF-alpha or anti-IgE antibodies may provide therapeutic tools for the treatment of TMA-induced CHS.