Albumin Adsorption and Retention on C18-Alkyl-Derivatized Polyurethane Vascular Grafts

The short-term albumin affinity and thrombo-resistance of a polyether polyurethane vascular graft have been improved. The method is based on the C18 alkylation of the polymer. Thrombus formation by a planimetric technique and albumin retention on wire-reinforced polyurethane tubes, both C18 alkylated and untreated, were measured in short-term (4-h) exposure at femoral arterial sites in the dog. 125I-Albumin was preabsorbed on tubes and then exposed to blood for successive 2-h periods. Albumin uptake on alkylated tubes prior to blood exposure and retention following 2 h of blood exposure were significantly greater than on controls. Following a fast desorption phase in blood, the remaining albumin was more slowly desorbed from alkylated than from control tubes. Reincubation with albumin and blood reexposure produced a similar tendency, suggesting blood conditioning does not reduce the albumin affinity-enhancing property of C18 alkylation in the short term. Blood-preconditioning experiments suggested endogenous albumin has a high affinity for the C18-alkylated surface. Scanning electron microscopic examination showed thrombus and platelet densities were higher on control than on alkylated surfaces. These results suggest in vivo albumin affinity is increased for C18-alkylated polyurethane, which may be linked to decreased thrombus formation on these surfaces.     

Polyether Synthesis through Reductive Etherification Reaction Strategy

The reductive etherification reaction (RER) of carbonyl groups (aldehydes or ketones) through silane as a reducing agent together with Bronsted or Lewis acid affords the synthesis of symmetrical and unsymmetrical ethers. This strategy is applied at the macromolecular level for the first time in 1993, and isophthalaldehyde is self-polymerized in the presence of triethylsilane (Et₃SiH)/ tritylperchlorate (TrClO₄) to yield polyethers with low to moderate molecular weights. Next, the polyethers with alternating structures are achieved by reacting isophthalaldehyde with bis(trimethylsilyl) ethers or diols as comonomers using reducing agent silane and Lewis acid. Moreover, in recent years, it is shown that polyether synthesis and post-polymerization modification (PPM) of polymers proceeds smoothly and effectively with the RER strategy in the presence of chlorodimethylsilane (CDMS), which acts as both a reducing agent and a Lewis acid.     

Reductive N‐alkylation of secondary amines with [2‐11C]acetone

The development of a labeling method for secondary amines with [2‐¹¹C]acetone is described since the R₂N‐isopropyl moiety is present in many biologically active compounds. The influence of a variety of parameters (e.g. reagents, solvents, temperature, and time) on the reaction outcome is discussed. Under the optimal reaction conditions, [¹¹C]1‐isopropyl‐4‐phenylpiperazine ([¹¹C]iPPP) was synthesized from [2‐¹¹C]acetone and 1‐phenylpiperazine in a decay‐corrected radiochemical yield of 72%. The overall synthesis time, from EOB to HPLC analysis of [¹¹C]iPPP, was 20 min. Specific activity was 142–208 GBq/μmol at the end of synthesis. Copyright © 2003 John Wiley & Sons, Ltd.     

Synthesis of [uniformly ring‐14C]‐labelled 4‐hydroxybenzaldehyde,vanillin, and protocatechualdehyde

[Uniformly ring‐¹⁴C]‐labelled 4‐hydroxybenzaldehyde, vanillin, and protocatechualdehyde were synthesized from [¹⁴C]‐labelled phenol, guaiacol, and catechol with methyl dichloromethyl sulfide (CH₃SCHCl₂) under Friedel–Crafts alkylation conditions in dichloromethane at ?78°C for 5 min (in the case of phenol and guaiacol) or at ?20°C for 1 min (in the case of catechol), by rapid addition of SnCl₄ to mixtures of the phenolic compound and CH₃SCHCl₂, followed by hydrolysis with HCl. Regioselective formylation (para to the –OH group) was achieved. The conversion rates were 96, 81, and 88% for 4‐hydroxybenzaldehyde, vanillin, and protocatechualdehyde, respectively, and the yields of the recovered products after work‐up amounted to 88, 75, and 83%, respectively. In the case of guaiacol, 17% of isovanillin was obtained as by‐product. It was found that the presence of water or ethyl acetate in the reaction mixture, at a molar ratio of 60:1 (water:guaiacol) or 120:1 (ethyl acetate:guaiacol), had little influence on the yields under the reaction conditions. Factors influencing the yields are discussed in the study. Copyright © 2004 John Wiley & Sons, Ltd.     

咪康唑和益康唑的PEG-400连续催化N-和O-烷基化反应制备

用氢氧化钠作碱,PEG-400为相转移催化剂,在THF中不经分离连续完成1-(2,4-二氯苯基)-2-氯乙醇的N-和O-烷基化反应,制得抗真菌剂硝酸咪康唑和硝酸益康唑,收率分别为63%和68%.     

An innovative quaternary ammonium methacrylate polymer can provide improved antimicrobial properties for a dental adhesive system

A quaternary ammonium methacrylate polymer (QAMP) with antimicrobial potential was synthesized. The resulting product (QAMP) was characterized by FTIR spectroscopy, NMR spectroscopy, visible spectrophotometry, XRPD and TGA. The in vitro susceptibility tests against Streptococcus mutans of QAMP were investigated prior and after incorporation into a commercial adhesive system (Clearfil? SE Bond). The release of quaternary ammonium compounds from the experimental adhesive system (Clearfil? SE Bond?+?5% QAMP) was performed during 1, 7, 14, 21 and 30 days. Spectroscopic data confirmed that QAMP was successfully obtained. Thermogravimetric analysis indicated that QAMP was heat stable. Prior incorporation into the adhesive system, QAMP revealed an inhibition halo of 18.33?±?0.6?mm. By agar disk diffusion test, Clearfil? SE Bond containing 5% QAMP presented an inhibition halo (16.67?±?1.5?mm) similar to Clearfil? Protect Bond (positive control, 17.00?±?1.7, p?=?0.815) and significantly higher than Clearfil? SE Bond (negative control, 11.00?±?1.0, p?=?0.006). The minimum inhibitory/bactericidal concentrations for Clearfil? SE Bond containing 5% QAMP were 20?μL?mL^?1. The release of quaternary ammonium compounds from the experimental adhesive containing QAMP was very low (5.1%) when compared to Clearfil? Protect Bond that released 47.2% of its quaternary ammonium monomer (MDPB) after 30 days. The QAMP can offer enhanced antimicrobial properties for self-etching adhesive systems.     

The discovery of new and more potent chloropyramine (C4) analogues for the potential treatment of invasive breast cancer

Breast cancer is the second most common cancer worldwide, accounting for 25% of all female cancers. Although the survival rate has increased significantly in the past few decades, patients who develop secondary site metastasis as well as those diagnosed with triple negative breast cancer still represent a real unmet medical challenge. Previous studies have shown that chloropyramine ( C4 ) inhibits FAK‐VEGFR3 signalling. More recently, C4 is reported to have SASH1 inducing properties. However, C4 exerts its antitumour and antiangiogenic effects at high micromolar concentrations (>100 μm ) that would not be compatible with further drug development against invasive breast cancer driven by FAK signalling. In this study, molecular modelling guided structural modifications have been introduced to the chloropyramine C4 scaffold to improve its activity in breast cancer cell lines. Seventeen compounds were designed and synthesized, and their antiproliferative activity was evaluated against three human breast cancer lines (MDA‐MB‐231, BT474 and T47D). Compound 5c was identified to display an average activity of IC₅₀ = 23.5–31.3 μm , which represents a significant improvement of C4 activity in the same assay model. Molecular modelling and pharmacokinetic studies provided more promising insights into the mechanistic features of this new series.     

复方甘草甜素联合还原型谷胱甘肽治疗48例抗结核药物性肝炎的疗效分析

目的　探讨复方甘草甜素和还原型谷胱甘肽对结核药物性肝炎的临床疗效。方法 采用前瞻性研究,对2001年1月—2004年12月诊断为抗结核药物性肝炎48例住院患者随机分为治疗组和对照组,前者予复方甘草甜素和还原型谷胱甘肽治疗,后者进行常规治疗,疗效进行χ²统计学分析。结果 结核药物性肝炎大多发生于强化期内,临床表现为恶心、呕吐,严重者出现乏力、纳差、黄疸、腹胀、肝区疼痛及肝大,复方甘草甜素和还原型谷胱甘肽的疗效显著优于对照组。结论 复方甘草甜素和还原型谷胱甘肽治疗1周内可明显改善药物性肝炎表现及恢复肝功能作用,对于结核药物性肝炎有较高疗效,而且临床应用安全。     

Evidence for an intermediate conformational state of LacY

LacY mutant Cys154 → Gly exhibits a periplasmic-closed crystal structure identical to the WT, but is periplasmic-open in the membrane. The mutant hardly catalyzes transport, but binds galactosides from either side of the membrane with the same affinity and is resistant to site-directed proteolysis relative to the pseudo-WT. Site-directed alkylation was also applied to 11 single-Cys mutants in Cys154 → Gly LacY in right-side-out membrane vesicles or after solubilization and purification in dodecyl-β-D-maltopyranoside (DDM). Unlike the pseudo-WT, Cys replacements on the periplasmic side of the Cys154 → Gly mutant label rapidly in the membrane without sugar, but labeling decreases markedly after the mutant proteins are purified. Thus, Cys154 → Gly LacY likely favors a higher-energy intermediate periplasmic-open conformation in situ, but collapses to a lower-energy periplasmic-closed conformation in DDM after purification. Notably, branched-chain or neopentyl glycol maltoside detergents stabilize Cys154 → Gly LacY in the membrane-embedded form.     

万古霉素N4氨基的还原烷基化条件优化

目的 优化万古霉素N4氨基还原烷基化的反应条件。方法 以万古霉素为原料,筛选还原烷基化反应的溶剂、还原剂、醛用量和反应温度,用HPLC方法测定原料和产物含量。结果 确立了以甲醇/二甲基亚砜=1:1为溶剂、硼烷叔丁胺为还原剂、1.3倍醛用量、缩合温度65℃、还原温度为室温的最优反应条件。结论 利用本文优化后的条件可以有效合成万古霉素N4氨基还原烷基化产物,研究结果为其他糖肽类抗生素的半合成衍生化提供技术基础。