The hypolipidemic activity of heterocyclic thiosemicarbazones, thioureas and their metal complexes in sprague dawley male rats

Heterocyclic thiosemicarbazones, thioureas and their copper, nickel, and cobalt complexes were shown to be potent hypolipidemic agents in male Sprague Dawley rats at 8 mg/kg/day, orally. These agents lowered the activity of rat hepatic rate limiting enzymes for the synthesis of cholesterol and triglycerides. The effects of these agnets on cytoplasmic ATP-dependent citrate lyase, acetyl CoA synthetase and HMG-CoA reductase activities were reduced by a magnitude to explain the reduction of serum cholesterol levels afforded by the compounds. The reduction of acetyl CoA carboxylase, sn-glycerol-3-phosphate synthetase and phosphotidylate phosphohydrolase activities caused by the derivatives is of sufficient magnitude to explain the observed reduction in serum triglycerides after administration of the agents.     

The hypolipidemic activity of metal complexes of amine carboxyboranes in rodents

The metal complexes of amine-carboxyborane including copper, chromium, zinc, calcium amd cobalt were effective hypolipidemic agents lowering both serum cholesterol and triglyceride levels significantly in mice at 8 mg/kg/day, I.P. after 16 days. The agents reduced acetyl CoA synthetase, ATP-dependent citrate lyase, acyl CoA cholesterol acyl transferase, sn-glycerol-3-phosphate acyl transferase activities of rat liver and small intestinal mucosa after 14 days treatment. The neutral cholesterol ester hydrolase activity was elevated by the agents in both tissues. The metal complexes altered lipid levels in the bile of rats after treatment as well as the bile acid composition after 14 days administration, orally. The agents blocked enterohepatic absorption of cholesterol from rat isolated intestinal loops.     

Boronated pyrimidines and purines as cytotoxic, hypolipidemic and anti-inflammatory agents

The simple boronated bases, e.g. cytosine, adenine and guanine, containing no sugar residues retained good pharmacological activity as hypolipidemic, anti-neoplastic and anti-inflammatory agents in mice at 8 mg/kg. Their activities were generally identical to their respective nucleoside derivatives. Interestingly the boronated acyclovir derivative was a very potent hypolipidemic agent achieving better activity than clofibrate and lovastatin. The boronated adenine derivatives appeared to have the best anti-inflammatory activity in reducing local edema and analgesic effects. The agents were active against the growth of murine and human leukemias and human HeLa-S(3) suspended uterine carcinoma. Only the boronated adenine derivatives were effective in blocking the growth of human SW480 adenocarcinoma and the KB nasopharynx.     

Structure–activity relationships in supported Au catalysts

Au-based catalysts have great potential because of their unique activity and selectivity for a variety of important reactions. The special catalytic properties of supported Au nano-particles depend critically upon the particle morphology, i.e. size, shape and thickness, as well as support effects. This paper reviews the current understanding of CO oxidation on supported Au catalysts. The electronic structure of Au particles at various nucleation sites and on different supports is summarized, and the effect these changes have on catalytic performance is discussed. Recent results from our laboratories have demonstrated the synthesis of well-ordered Au mono- and bi-layer films on a titanium oxide support and show that the active Au structure for CO oxidation is an electron-rich, Au bi-layer. In contrast, the monolayer structure, which may involve the TiO_x support, is significantly less active (by less than an order of magnitude) than the Au bi-layer. The oxidation state of the Au and how this relates to the catalytic activity are also discussed.     

The hypolipidemic activity of boronated nucleosides in male mice and rats

The boronated nucleosides with varying bases and sugar moieties were shown to be potent hypolipidemic agents in rodents. The 3'- aminocynaoborane dideoxythymidine derivative caused reductions in serum cholesterol and triglyceride levels, tissue lipids, VLDL and LDL cholesterol levels while elevating HDL cholesterol levels in rodents. The agents suppressed rat hepatic acetyl CoA synthetase, HMG-CoA reductase, acyl-CoA cholesterol acyl transferase, phosphatidylate phosphohydrolase and lipoprotein lipase activities while elevating cholesterol-7alpha-hydroxylase activity from 25 to 100 muM.     

芳香醛(酮)缩氨基硫脲的微波合成及其抗菌活性的研究

肼基二硫代甲酸甲酯与相应的醛或酮在微波辐射下经2~3.5 min反应,得到3-二取代甲(乙)撑肼基二硫代甲酸甲酯,产率91%~96%。再与胺在微波辐射下经35~45 min反应,得到目标化合物,产率80%~90%。合成的6个目标化合物通过熔点测定和质谱、红外光谱、核磁共振氢谱分析,对其结构进行确证,并测试了化合物的抑菌活性。     

硫代-4-色满酮类缩氨基硫脲的微波合成及其抗菌活性研究

在微波无溶剂辐射条件下,以硫代-4-色满酮和取代氨基硫脲为原料,通过中性Al2O3催化,设计并高产率的合成了标题化合物,其结构经1HNMR、IR、ESI-MS和元素分析表征。相较于传统方法,微波干法大大缩短反应时间,极大程度提高产率,是一种绿色友好的合成方法。通过抗菌活性测试对其抑菌效果进行研究,结果表明,目标物对所试的部分菌种具有较强的抑制作用。     

Structure activity relationships of monocyte chemoattractant proteins in complex with a blocking antibody

Monocyte chemoattractant proteins (MCPs) are cytokines that direct immune cells bearing appropriate receptors to sites of inflammation or injury and are therefore attractive therapeutic targets for inhibitory molecules. 11K2 is a blocking mouse monoclonal antibody active against several human and murine MCPs. A 2.5 A structure of the Fab fragment of this antibody in complex with human MCP-1 has been solved. The Fab blocks CCR2 receptor binding to MCP-1 through an adjacent but distinct binding site. The orientation of the Fab indicates that a single MCP-1 dimer will bind two 11K2 antibodies. Several key residues on the antibody and on human MCPs were predicted to be involved in antibody selectivity. Mutational analysis of these residues confirms their involvement in the antibody-chemokine interaction. In addition to mutations that decreased or disrupted binding, one antibody mutation resulted in a 70-fold increase in affinity for human MCP-2. A key residue missing in human MCP-3, a chemokine not recognized by the antibody, was identified and engineering the preferred residue into the chemokine conferred binding to the antibody.     

The anti-inflammatory activity of boron derivatives in rodents

Acyclic amine-carboxyboranes were effective anti-inflammatory agents in mice at 8 mg/kg x 2. These amine-carboxyboranes were more effective than the standard indomethacin at 8 mg/kg x 2, pentoxifylline at 50 mg/kg x 2, and phenylbutazone at 50 mg/kg x 2. The heterocyclic amine derivatives as well as amine-carbamoylboranes, carboalkoxyboranes, and cyanoboranes were generally less active. However, selected aminomethyl-phosphonate-N-cyanoboranes demonstrated greater than 60% reduction of induced inflammation. The boron compounds were also active in the rat induced edema, chronic arthritis, and pleurisy screens, demonstrating activity similar to the standard indomethacin. The compounds were effecive in reducing local pain and decreased the tail flick reflex to pain. The derivatives which demonstrated good anti-inflammatory activity were effective inhibitors of hydrolytic lysosomal, and proteolytic enzyme activities with IC(50) 50 values equal to (-6)M in mouse macrophages, human leukocytes, and Be Sal osteofibrolytic cells. In these same cell lines, the agents blocked prostaglandin cyclooxygenase activity with IC(50) values of (-6)M. In mouse macrophage and human leukocytes, 5' lipoxygenase activity was also inhibited by the boron derivatives with IC(50) values of 10(-6)M. These IC(50) values for inhibition of these enzyme activities are consistent with published values of known anti-inflammatory agents which target these enzymes.     

新型有机硅多元胺环氧树脂固化剂结构与性能

评价了3种有机硅多元胺APS、SFA和PSPA分别固化环氧树脂E51(DGEBA)时,固化物的力学性能和粘接强度,并与常见脂肪胺类固化剂[乙二胺、己二胺、聚醚胺(D-230)]作了对比。固化物基体力学和热性能测试表明,有机硅多元胺环氧固化物表现出较佳的冲击强度、弯曲强度和热稳定性。有机硅多元胺/环氧树脂胶粘剂的铁片粘接强度以及耐水性明显高于脂肪胺/环氧胶粘剂体系,其中含苯基有机硅多元胺作为固化剂时粘接强度最高,达到14.8 MPa。()     

Hypolipidemic activity of amine-borane aducts of cyclohexylamine and toluidine in rodents

The amine-borane adducts of cyclohexylamine and toluidine were observed to be potent hypolipidemic agents in mice, I.P. and rats orally at 8 mg/kg/day lowering both serum cholesterol and triglyceride levels after 14-16 days. These compounds were able to lower tissue lipids including the cholesterol content of the aorta wall. The agents successfully lower VLDL- and LDL-cholesterol content while elevating HDL-cholesterol content significantly. The agents also modulate lipid regulatory enzyme activities in a manner to reduce liver lipid levels. These studies demonstrate that the nitrogen atom does not have to be apart of the aromatic ring as in heterocyclic-amine borane to afford good hypolipidemic activity in rodents.     

Hypolipidemic activity of the surfactants aminimides,and their effects on lipid metabolism of rodents

A series of short chain fatty acid derivatives of aminimides were shown to possess hypolipidemic activity in rats and mice. Most of the agents tested lowered both serum cholesterol and triglyceride levels by at least 30% in mice and were effective in hyperlipidemic induced mice. 1,1-Dimethyl-1-(2-hydroxypropyl)-amine mersitimide lowered serum cholesterol levels 41% and serum triglyceride levels 56% at 20 mg/kg/day I.P. after 16 days. The same agent was active orally when administered to rats with a 38% reduction in serum cholesterol and a 52% reduction in serum triglycerides after 14 days. The agents inhibited liver acetyl CoA synthetase, ATP dependent citrate lyase and phosphatidate phosphohydrolase activities in vitro and in vivo. Reduction of cholesterol, triglycerides, neutral lipids and phospholipid levels were noted in the livers of mice treated for 16 days. In rat studies, cholesterol, triglyceride and phospholipid levels were reduced in liver, small intestine and the feces after two weeks' dosing. The cholesterol content was reduced in the very low density lipoprotein (VLDL) and low density lipoprotein (LDL) fractions but elevated in the high density lipoproteins (HDL). Triglyceride levels were lowered in the VLDL, and neutral lipid levels were reduced in the chylomicron and VLDL fractions.     

Inhibition of sunfish feeding by defensive steroids from aquatic beetles: Structure activity relationships

The vertebrate hormone deoxycorticosterone is the most commonly occurring component of defensive secretions from aquatic beetles in the family Dytiscidae. Deoxycorticosterone and the structurally related steroids pregn-4-en-20:-ol-3-one and pregn-4-en-20-ol-3-one were tested for their ability to inhibit feeding by bluegill sunfish,Lepomis macrochirus, in laboratory assays. Deoxycorticosterone at oral doses of 660g (2 x 10^–6 mol) per pellet caused 94% inhibition in the acceptance of artificial food pellets. At the same molar dosage, pregn-4-en-20-ol-3-one inhibited food consumption by 58%, while its epimer, pregn-4-en-20-ol-3-one, did not significantly inhibit feeding. These results indicate that specific stereochemical conditions must be satisfied for the pregnenes to be noxious toL. macrochirus and suggest the existence of a receptor-ligand interaction. The potency of the three steroids in assays of feeding inhibition contradicts earlier results based on toxicity and anesthetic assays in which fish were immersed in solutions of steroids.     

Anti-inflammatory activity of (polyphenolic)-sulfonates and their sodium salts in rodents

A series of polyphenolic-sulfonated compounds were observed to have potent anti-inflammatory activity and were protective against induced endotoxic shock in mice at 8 and 16 mg/kg, I.P. These agents proved to be potent elastase inhibitors in human leukocytes and J774-AI and IC-21 mouse macrophages as well as prostaglandin cyclo-oxygenase inhibitors in J774-AI macrophages. The compounds from 5 to 50 muM inhibited TNFalpha release from IC-21 macrophages and IL-1 release from mouse P388(D1) macrophages induced by LPS. The binding of these cytokines to high affinity receptors on target cells, e.g. L929 fibroblasts and IL-2 in HuT78 T lymphoma cells, were also suppressed by the agents. These compounds blocked the adhesion of leukocytes and macrophages to the plasma membranes of L929 fibroblasts.     

Structure/permeability relationships of polyamide-imides

Structure/permeability correlations for a family of aromatic polyamide-imides are presented. The variations in chemical structure lead to significant changes in permeability. The crystallization of PAP results in a very low permeability. The introduction of bulky group tends to increase permeability without a corresponding decrease in permselectivity. This result contributes to the inhibition of chain packing and segmental mobility. Wide-angle X-ray diffraction measurements of average segmental spacing of the materials and fractional free volume calculations characterize the packing of the different polymers. © 1994 John Wiley & Sons, Inc.     

Peptide dendrimers as artificial enzymes, receptors, and drug-delivery agents

The dendritic architecture applied to peptides provides a practical entry into globular macromolecules resembling proteins. A modular design was chosen using a divergent synthesis on solid support alternating proteinogenic alpha-amino acids with branching diamino acids, producing peptide dendrimers with a molecular weight of 3-5 kDa. Initial studies focused on models for hydrolases and produced esterase peptide dendrimers featuring histidine as the key catalytic residue. Variations of amino acid composition and the branching diamino acid led to enantioselective catalysts. Rate accelerations of k(cat)/k(uncat) = 90,000 were obtained when the design was changed to monomeric peptide dendrimers alternating two amino acids with the branching unit. A combinatorial approach was developed allowing for the preparation of large libraries (>60,000 members), which were screened for B12 binding and catalytic activity. The peptide dendrimers were also investigated for drug delivery. Glycopeptide dendrimers conjugated to colchicine selectively inhibited the proliferation of targeted cells, whereas colchicine alone displayed high toxicity.     

Aromatic amino acids as latent,bio-based curing agents and toughening agents for epoxy resins

In the realm of bio-based curing agents, recent investigations have focused on amino acids owing to their distinctive attributes. Nevertheless, the suitability of thermosets cured with aromatic amino acids as latent matrix materials for fiber-reinforced composites remains to be empirically established. Consequently, this study is oriented toward assessing the mechanical properties of diglycidyl ether of bisphenol A when cured with either L-tryptophan or L-tyrosine, in the presence of a latent, urea-based accelerator. The investigated properties include glass transition temperatures, tensile, flexural, compression, and fracture toughness properties. The predominant variations in the mechanical characteristics of these thermosets are confined to their Young's moduli and fracture toughness properties. This divergence is attributed to the greater presence of crystals in the L-tyrosine-cured thermoset, resulting in enhanced reinforcement and toughening effects compared to the L-tryptophan-cured thermoset.     

Synthesis, antiproliferative activity, and structure-activity relationships of 3-aryl-1H-quinolin-4-ones

The antiproliferative activities of 36 3-aryl-1H-quinolin-4-ones were determined against two cancer cell lines (Hep G2 and KB) in vitro. The results indicate that most of these compounds show good cytotoxic activity against human cancer cell lines, but no cytotoxicity against a human normal cell line (L02). The positive control compounds genistein and 5-fluorouracil show no selectivity at inhibiting the growth of the above three cell lines. Generally, compounds that bear a halogen atom at the 8 position and a methoxy group at the 3' position exhibited remarkable cytotoxicity toward human cancer cell lines. Electron-withdrawing substituents at the 6 position decrease the antiproliferative activity significantly. We also put forward a pharmacophore model for 3-aryl-4-quinolinones binding with epidermal growth factor receptor protein tyrosine kinases (EGFR PTK). Out of the 36 synthetic compounds, 34 are reported for the first time.     

Cellulosic materials: Structure and enzymatic hydrolysis relationships

Structural and morphological features of four different cellulosic materials have been deeped by X-ray, CP–MAS NMR, water retention, and specific surface area analysis. Hydrolysis time courses of two of these celluloses were followed by employing an enzymatic system consisting of a cellulase from Trichoderma viride and a cellobiase from Aspergillus niger. Experimental results were rationalized on the basis of a methematical model previously verified on the other two substrates. All the celluloses presented the same mechanistic framework involving product inhibitions. The most efficient pretreatment was found to be the dissolution of cellulosic material in the dimethyl sulfoxide–paraformaldehyde system and regeneration with ammonia. This treatment cancelled the memory of the initial structural order.