鬼臼毒素类新药的研发思路

Study on the development of podophyllotoxin related new drugs

鬼臼毒素是有一定药效活性的环木脂内酯,具有抗肿瘤、抗病毒、抗风湿、杀虫等活性。其中,抗肿瘤活性最引人关注,常常作为研究开发抗肿瘤药物的先导化合物。但鬼臼毒素水溶性差、易产生多药耐药性和毒性较强等缺点限制了它的临床应用,因此通过结构修饰寻找高效低毒的鬼臼毒素衍生物是鬼臼毒素类化合物研究的重点。本文介绍鬼臼毒素衍生物的药效团模型、构效关系模型以及当前对鬼臼毒素进行结构修饰的研究思路。

Podophyllotoxin is cyclolignolide that has some pharmacological activities , and it is known to have various functions and bioactivities such as antitumor , antivirus, anti-rheumatism and insecticide.Among them, the antitumor activity of podophyllotoxin is widely noted , so that it is taken as a lead compound in drug discovery of anticancer .However, there are some drawbacks, for example poor water solubility, easy to produce multidrug resistance and strong toxicity , these all li-mit its clinical application.So the focus of research is to find efficient and low toxicity of podophyllo -toxin derivatives through the structure modification .This paper introduces the pharmacophore model and quantitative structure activity relationships (QSAR) model of podophyllotoxin, and the research approach about its structure modification .