Comparative haemolytic activity of bis(phenylmethyl) disulphide, bis(phenylethyl) disulphide and bis(phenylpropyl) disulphide in rats.

Thiols and disulphides make an important contribution to the organoleptic characteristics of foodstuffs, and many such compounds are approved for use as food flavours. Some thiols and disulphides are haemolytic agents in vivo. The haemolysis is caused by oxidative damage to erythrocytes initiated by "active oxygen" species formed during redox cycling between the thiol and disulphide. In all cases so far examined, the haemolytic activity of a thiol or disulphide in vivo is correlated with its ability to cause oxidative damage to red cells in vitro. In the present study, the in vitro and in vivo effects of three aryl-alkyl disulphides have been compared. Bis(phenylmethyl) and bis(phenylpropyl) disulphide induced no oxidative damage in vitro, and, as expected, caused no haemolysis in rats. In contrast, bis(phenylethyl) disulphide, while causing little or no oxidative damage in vitro, was a potent haemolytic agent in vivo. It is suggested that this effect is due to dehydrogenation of the ethyl disulphide to the ethenyl derivative in vivo. Bis(phenylethenyl) disulphide was found to cause extensive oxidative damage to red cells in vitro and severe haemolytic anaemia in rats. The results of this study show that the in vivo toxicity of thiols and disulphides cannot always be predicted on the basis of their effects in vitro.     

Discovery of novel alkylated (bis)urea and (bis)thiourea polyamine analogues with potent antimalarial activities

A series of alkylated (bis)urea and (bis)thiourea polyamine analogues were synthesized and screened for antimalarial activity against chloroquine-sensitive and -resistant strains of Plasmodium falciparum in vitro. All analogues showed growth inhibitory activity against P. falciparum at less than 3 μM, with the majority having effective IC(50) values in the 100-650 nM range. Analogues arrested parasitic growth within 24 h of exposure due to a block in nuclear division and therefore asexual development. Moreover, this effect appears to be cytotoxic and highly selective to malaria parasites (>7000-fold lower IC(50) against P. falciparum) and is not reversible by the exogenous addition of polyamines. With this first report of potent antimalarial activity of polyamine analogues containing 3-7-3 or 3-6-3 carbon backbones and substituted terminal urea- or thiourea moieties, we propose that these compounds represent a structurally novel class of antimalarial agents.     

Stereoselective antitumor properties in the Lewis lung carcinoma model using bis(morpholinomethyl) derivatives of tricyclic bis(dioxopiperazines)

Geometric isomers of 2,11-bis(morpholinomethyl)tetrahydrodipyrazino[1,2-a:2',1'-c]pyraz ine-1, 3,10,12-(2H,4H,9H,11H)-tetrone (3 and 4) and the parent bisimides (1 and 2) were studied for their stereoselective antimetastatic activity in the Lewis Lung carcinoma model. The morpholinomethyl cis-syn-trans isomer 4 was more effective as an inhibitor of metastasis than the other three analogues. Using a postamputation protocol, the order of decreasing activity was cis morpholinomethyl analogue 4 greater than trans morpholinomethyl analogue 3 greater than parent cis imide 2 greater than parent trans imide 1. Increased activity observed for the morpholinomethyl derivatives may reflect differences in solubility and delivery (prodrug) or an intrinsic antitumor activity of the morpholinomethyl-N functionality.     

青蒿素类似物的研究 Ⅶ.双(二氢青蒿素)醚和双(二氢脱氧青蒿素)醚类化合物的合成

Some ethers, of bis(dihydroqinghaosu) Ⅲ and bis(dihydrodeoxyqinghaosu) Ⅳ were prepared in order to study the structure-activity relationships and to search for new antimalarials. Compounds Ⅲ were sythesized by condensation of glycol with two moles of dihydroqinghaosu using boron trifluoride etherate as catalyst. Compounds Ⅳ were prepared from ethers of bis (dihydroqinghaosu) by reduction with zinc and acetic acid.The bis-ethers were evaluated against chloroquine-resistant strain of plasmodium berghei in mice. Compounds Ⅲ were less potent than methyl-dihydroqinghaosu (Ⅰ) and compounds Ⅳ were inactive.     

Embryotoxic evaluation of bis(tri-n-butyltin)oxide (TBTO) in mice

Pregnant mice were treated on days 6–15 of gestation with 5, 20 and 40 mg/kg/d bis (tri-n-butyltin)oxide (TBTO), and sacrificed on gestational day 17. At the highest dose TBTO caused a significant reduction of maternal body weight gain and also proved to be highly embryotoxic. Necropsy showed a dose-related decrease in spleen weight while a dose-dependent increase in placental weight was observed.     

Antimicrobial activity of bis(1,2,3-triazole) derivatives

Translated from Khimiko-Farmatsevticheskii Zhurnal, No. 10, pp. 52–53, October, 1991.     

双联苄类化合物结构多样性的研究进展

目的对双联苄类化合物结构多样性进行综述。方法查阅国内外相关文献29篇,从生源合成、旋阻异构和化学合成三方面介绍双联苄类化合物的结构多样性。结果与结论双联苄化合物是光学活性奇特的天然产物,其结构类型多样,深入研究其结构特征,对理解这类天然产物的构效关系的研究和生物合成都具有指导性作用。     

2,2’-二氟-6,6’-双(二苯基膦)联苯的合成

２，２’－二氟－６，６’－双（二苯基膦）联苯是一种极具吸引力的、缺电子的过渡金属催化剂的配体。本文用三步反应合成了这个配体（总收率为５３％）。比原文献报道的四步反应及４９％总收率的方法有了改进。其结构为ＩＲ，ＭＳ及ＮＭＲＩ所证实。     

双(α-呋喃甲酸)氧钒的胰岛素样作用

钒作为人体必需的微量元素,在葡萄糖的代谢过程中起着重要作用.大量的体内外研究表明微量元素钒具有"胰岛素样(insulin-mimics)"作用,研究表明它能增加胰岛素的敏感性,是"胰岛素的促进剂(insulin-enhancing agent)",可用于治疗和缓解1型和2型糖尿病.