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新型吡唑并吡唑类化合物的合成、抗 HCV 和抗肿瘤活性。

New pyrazoles incorporating pyrazolylpyrazole moiety: synthesis, anti-HCV and antitumor activity.

机构信息

Department of Chemistry, Faculty of Science, University of Cairo, Giza 12613, Egypt.

出版信息

Eur J Med Chem. 2010 Mar;45(3):1042-50. doi: 10.1016/j.ejmech.2009.11.050. Epub 2009 Dec 5.

Abstract

Three series of novel pyrazole derivatives 2b-d, 4a-d and 6a-d were synthesized via two step procedure that utilizes hydrazonoyl chlorides 1a-d and enaminones 3a-d and 5a-d, respectively as starting materials. The structures of all the newly synthesized products have been established on the basis of analytical and spectral data. Moreover, some of the products 2-6 were tested against HCV and Subacute Sclerosing Panencephalitis (SSPE). In addition, compounds 2-6 were also tested for the inhibition of peroxynitrite-induced tyrosine nitration and antioxidant activity. The tested compounds are highly effective at very low concentration as anti-HCV, SSPE antioxidant and anticancer in the following ascending order 2d, 4c, 6b, 3b, 6c, 4d, 2b, 2c, 2a, 6a, 5b, 5a, 3a, 4b and 5c. It is worth to mention that all tested compounds are more potent than the reference standards used for comparing activity. All the measurements revealed that the mechanism of action of the anti cancer activities of all the tested compounds is topoisomerase I inhibitor.

摘要

通过两步法合成了三系列新型吡唑衍生物 2b-d、4a-d 和 6a-d,分别利用肼酰氯 1a-d 和烯胺酮 3a-d 和 5a-d 作为起始原料。所有新合成产物的结构均基于分析和光谱数据确定。此外,一些产物 2-6 还针对 HCV 和亚急性硬化性全脑炎 (SSPE) 进行了测试。此外,还测试了化合物 2-6 对过氧亚硝酸盐诱导的酪氨酸硝化和抗氧化活性的抑制作用。在以下递增顺序中,测试化合物在非常低的浓度下对 HCV、SSPE 抗氧化和抗癌具有非常高的效果:2d、4c、6b、3b、6c、4d、2b、2c、2a、6a、5b、5a、3a、4b 和 5c。值得一提的是,所有测试的化合物都比用于比较活性的参考标准更有效。所有测量结果表明,所有测试化合物的抗癌活性的作用机制是拓扑异构酶 I 抑制剂。

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