一种孕激素受体拮抗剂先导化合物的分子对接研究  

Docking Study of a Progesterone Antagonist Lead Compound

作　　者：胡健[1,2] 刘嘉茵[1,2] 

机构地区：[1]中国药科大学生命科学与技术学院,江苏南京210009 [2]南京医科大学第一附属医院生殖医学国家重点实验室,江苏南京210029

出　　处：《药物生物技术》2015年第5期421-424,共4页Pharmaceutical Biotechnology

摘　　要：双酚A（bisphenol A，BPA）是一种常见的内分泌干扰物，对人类具有多重影响。其代谢产物具有更强的受体结合能力，如4-甲基-2，4-二（4-羟苯基）-戊-1-烯（MBP）对雌激素受体的结合能力比双酚A高3～4个数量级。某些芳香族β-氨基酮衍生物的结构与MBP类似，并且对孕激素受体具有程度不等的竞争性抑制作用。该课题采用分子对接方法计算了MBP与孕激素受体的结合自由能并与芳香族β-氨基酮衍生物相对照，结果表明MBP具有与芳香族β-氨基酮衍生物类似的结合能力，有必要在后续的研究中探索其竞争性抑制的作用机理并考虑其作为新型非甾体类孕激素抑制剂先导化合物的可能性。Bisphenol A（BPA） is an ubiquitous endocrine disrupter,which has mukiple effects on human beings. Some of its metabolites have stronger binding affinity than the parent compound. 4-methyl-2,4-bis （4-hydroxyphenyl）-pent-1-ene （MBP） is a compound of this kind, whose binding affinity to the estrogen receptor is 1 000-10000-fold higher than BPA. Some aromatic β-aminoketone derivatives are proved to have antagonism on progesterone receptor, and MBP is structurally similar to these compounds. In this study, molecule docking method was used to calculate the free binding energies of MBP and selected β-amino-ketone derivatives to the human progesterone receptor and the binding modes were also compared. The results showed that the binding affinity of MBP was very similar to some β-amino-ketone derivatives, which indicated that MBP may have strong binding affinity to human progesterone receptor. Further molecular modification should be carried out to explore the antagonist effect of MBP, and its possibility was considered as a lead compound of new type of non-steroidal progesterone antagonist.

关 键 词：双酚A代谢物 芳香族β-氨基酮衍生物 孕激素受体 分子对接 

分 类 号：Q7[生物学—分子生物学]