Cytotoxic di(8-quinolyl) disulfides

It has been shown that the nature of the substituent and its position in the quinoline ring markedly affects the antitumor activity and toxicity of di(8-quinolyl) disulfides. The greatest cytotoxicity in the series of methyl derivatives was shown by the 7-, 6-, and 3-isomers towards HT-1080 (human fibrosarcoma) and MG-22A (mouse hepatoma) tumor cells while the 2-methyl derivatives generally have no effect on these cells. High cytotoxicity was also shown (LC₅₀ <1 μg/ml) by other 7-substituted compounds (Cl, PhO, PhS) but they also appear to be highly toxic towards normal NIH 3Y3 mouse embryonic fibroblasts. A similar trend was observed in the series of 5-substituted compounds (NH₂, Cl, OMe, NO₂) which were highly active towards tumor cells but were toxic to normal cells. The best selectivity was found for the 6-substituted quinolines, the 6-methoxy derivative at low concentration brought about the death of tumor cells but appeared much less toxic towards normal fibroblasts (LC₅₀ 100 μg/ml with a corresponding LD₅₀ of 874 mg/kg ). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 750–754, May 2007.     

Synthesis and cytotoxicity of metal 4-methyl-8-quinolinethiolates

It has been shown that the introduction of a methyl group at position 4 of the quinoline ring in metal 8-quinolinethiolates brings about a significant increase in the selectivity of their cytotoxic activity. It was found that rhodium 4-methyl-8-quinolinethiolate is 46 times less toxic than the unsubstituted 8-quinolinethiolate but with comparable toxicity towards MG-22A tumor cells (LC₅₀ 2 μg/ml). __________ Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 5, pp. 755–758, May, 2007.     

Protective effect of Epicatechin on APAP-induced acute liver injury of mice through anti-inflammation and apoptosis inhibition

Abstract

Epicatechin (EC) is the most effective compound in Euonymus alatus (Thunb.)Sieb, and possesses a series of benefits, including anti-inflammatory, antioxidant, antiobesity and anticancer effects. In this study, we investigated the protective effects of EC in Acetaminophen(N-acetyl-p-aminophenol, APAP)-induced acute liver injury in C57BL/6J mice and explored the possible mechanisms involved in these effects.

     

FTIR study of zinc-induced biochemical changes in the liver of Indian carp <Emphasis Type="Italic">Labeo rohita</Emphasis>

Zinc is an essential metal for different physiological functions and becomes toxic when elevated concentrations are introduced into the environment. In the present study, an attempt is made to analyze zinc-induced biochemical changes in the liver tissues of freshwater fingerlings of Labeo rohita using Fourier Transformation Infrared Spectroscopy. Several important features have been observed in the FTIR spectra of zinc-intoxicated liver tissues, namely, altered membrane lipid, altered protein profile, and increased glycogen content, indicating an alteration in the lipid and protein profiles leading to modification in membrane composition. Further, it is observed that acute exposure to zinc causes some alteration in protein profile with a decrease in α-helix and an increase in random coil structure. Treatment with the chelating agent D-penicillamine reduces the biochemical contents in the liver tissues. This shows that D-penicillamine is a good antidote for zinc toxicity. Published in Zhurnal Prikladnoi Spektroskopii, Vol. 75, No. 5, pp. 746–752, September–October, 2008.     

吲哚衍生物类VEGFR-2酪氨酸激酶抑制剂的从头设计

以血管内皮生长因子受体-2(VEGFR-2)酪氨酸激酶的晶体结构为基础, 采用从头药物设计方法, 设计了一系列吲哚类化合物, 并用类药性和分子对接进行了筛选, 最后得到10个对接能量较低的化合物分子, 对具有最低结合能的化合物与VEGFR-2酪氨酸激酶的复合物进行了10 ns的分子动力学模拟, 并对其结合模式进行了分析. 这些化合物结构新颖, 可能作为抗肿瘤的先导化合物或候选药物. 本文结果为VEGFR-2酪氨酸激酶抑制剂的进一步改造、 设计及合成提供了理论基础, 并有助于开发高活性和高选择性的抗肿瘤药物.     

拓展浓度加和模型预测三种三嗪类除草剂混合物的时间依赖毒性

浓度加和(CA)模型是评估与预测化学混合物毒性效应的常用模型之一,已广泛应用于药物组合与农药混配等多个混合物体系. 然而,CA不能用于包含不同时间具有不同效应组分的混合物体系,需要拓展. 以具有不同时间依赖毒性特征的三种三嗪类除草剂即嗪草酮(MET)、西草净(SIM)和环嗪酮(HEX)为混合物组分,以直接均分射线法(EquRay)构建它们的二元混合物,以青海弧菌Q67为受试生物,在6个不同时间(即0.25,2,4,8,12和16 h)下测定各混合物组分及其二元混合物暴露于Q67时的发光抑制毒性,分析与归纳抑制毒性随时间的变化规律. 结果表明,三种除草剂对发光菌Q67的发光抑制毒性具有不同的时间变化规律：MET的毒性随时间延长有明显增大的趋势,SIM的毒性在不同时间没有显著性变化,而HEX随着时间的延长毒性开始有所增加,而后变化很小;二元混合物毒性的时间变化规律与混合物组分有关,MET与HEX的二元混合物体系的毒性随暴露时间的延长而逐步增加,MET-SIM体系开始有所下降而后缓慢增加,而SIM-HEX体系的毒性在不同时间差异不明显;应用拓展后的CA模型分析所有二元混合物在不同时间点的毒性变化,表明都是加和的,没有协同或拮抗作用.     

中药定清片联合化疗治疗急性白血病复发的临床研究

目的: 观察中药定清片联合化疗与单纯化疗比较治疗急性白血病复发患者的临床疗效. 方法: 采用随机对照研究方法, 将符合纳入标准的60例急性白血病复发病例分为2组, 每组30例. 分别给予定清片联合化疗(试验组)或单纯化疗(对照组)治疗, 观察比较两组治疗前后的骨髓缓解率、血常规变化、中医证候疗效、感染发生率和不良反应发生情况. 结果: 试验组获完全缓解13例、部分缓解6例, 总缓解率63.33%; 对照组获完全缓解12例、部分缓解5例, 总缓解率56.67%, 两组的骨髓总缓解率相比较无明显统计学差异(P＞0.05). 在治疗后, 试验组的白细胞和血小板计数高于对照组, 两者比较有统计学差异(P＜0.05). 在中医证候疗效方面, 试验组的总有效率86.6%, 明显高于对照组的66.7%(P＜0.05). 在疗后的感染发生率和不良反应发生情况比较中, 试验组低于对照组, 两组间比较均有统计学差异(P＜0.05). 结论: 中药定清片联合化疗治疗急性白血病复发患者, 在西医疗效上与单纯化疗组无明显差异, 但联合治疗更利于化疗后白细胞及血小板的恢复以及减少感染及相关并发症的产生, 所产生的不良反应也低于单纯化疗组; 在中医证候疗效上联合治疗也优于单纯化疗组.     

Synthesis of Nonionic Oligomeric Manganese(Ⅱ) Complexes and Investigation of Their Toxicity and Τ1-Relaxation Enhancement

Six nonionic oligomeric manganese(Ⅱ) complexes with oligomeric phosphate-polyglycol-EDTA ester ligands were synthesized and characterized. The longitudinal relaxivities of these complexes were measured. One of these complexes, which showed the highest relaxivity, was chosen to be used in the acute toxicity test and the Τ1-weighted imaging experiment. It has been found that compared to Gd-DTPA, this nonionic oligomeric Mn(Ⅱ) complex exhibits no acute toxicity, generates highly enhanced MRI signals and increases the intention time in the rat liver tissue.     

Determination of macronutrients,micronutrients, non-essential elements in milk based-infant formulas by atomic absorption and inductively coupled plasma-optical emission spectroscopy after microwave and ultrasound assisted digestion

Microwave and ultrasound procedures for samples preparations were adopted and the elements were determined by validated flame atomic absorption and inductively coupled plasma–optical emission spectrometry. Student’s t-test was established whether there was a difference between the sample preparation methods. Trueness of certified values by all methods was ensured which were not differing significantly at 95% level of confidence interval. The highest intensity ratio of magnesium (II)/magnesium (I) was obtained at 1120 radiofrequency value to achieve accurate and reproducible results by inductively coupled plasma–optical emission spectrometry. The value of corresponding correlation coefficient (r²) were obtained as >0.990 indicating the excellent linearity for concentration range chosen for each element to be determined in commercial samples. Results showed that concentrations of calcium, magnesium, potassium, sodium, chromium, copper, iron, manganese, selenium, and zinc found in commercially available products are in good agreement with label as declared by the manufacturers. Exposure to aluminum, cadmium, and lead from consumption of products under evaluation was estimated and it was in compliance with permissible level suggested by European Commission regulations. Regarding the food safety monitoring, the proposed methods are rapid and met green chemistry approach so that can be implemented in laboratories easily for routine analysis.     

应用于水溶液介质中喹啉氧化的电芬顿工艺实验设计方法(英文)

采用碳毡阴极和铂阳极的电芬顿工艺研究了喹啉模型分子8-羟基喹啉硫酸盐（8-HQS）在水溶液介质中的降解行为. 由于电化学诱导芬顿药剂（H2O2,Fe2+）产生大量的羟基活性基（OH）,成为与有机物发生反应直到有机物完全矿化的强有力氧化剂,因此,电芬顿工艺具有很强的氧化能力. 采用正交实验设计确定了水溶液介质中8-HQS降解的操作参数. 结果表明,电流密度和8-HQS的初始浓度是影响降解速度的主要因素. 8-HQS浓度随着电解时间而减少,说明8-HQS的氧化遵循准一级反应动力学. 通过竞争动力学方法确定的由OH引起8-HQS氧化的绝对反应速度常数为1.62×109 mol^-1·L·s^-1. 通过Doehlert 矩阵研究了8-HQS矿化的最佳实验参数,由此确定最佳条件下电芬顿工艺能导致8-HQS在水溶液中的准完全矿化（总有机成分去除率95%）. 对8-HQS水溶液的处理,使得8-HQS矿化前的最终产物为短链羧酸. 同时研究了电芬顿处理中短链羧酸的演变行为. 溶液毒性演变的跟踪研究发现,中间产物的毒性比8-HQS强,但溶液的毒性在中间产物矿化后可以完全消除.