核苷酸还原酶抑制剂的定量构效关系  

Studies on the quantitative structure activity relationshipsof ribonucleotide reductase inhibitors

作　　者：罗一帆[1,2] 许旋[1,2] 谢宗江[1,2] 

机构地区：[1]中山医科大学天然药物研究室 [2]华南师范大学化学系

出　　处：《癌症》1998年第6期407-409,共3页Chinese Journal of Cancer

摘　　要：目的：从电子水平上探讨具有抗肿瘤活性的核苷酸还原酶抑制剂的定量构效关系（ＱＳＡＲ）。方法：用ＣＮＤＯ／２量化方法计算了３２个异羟肟酸化合物、５个酰胺化合物和７个羧甲酯类化合物的电子结构，对化合物的量化指数与其对核苷酸还原酶半抑制量的负对数值ＰＣ进行了逐步回归。结果：得到关于异羟肟酸化合物（第一组），酰胺化合物和羧甲酯类化合物（第二组）的两个ＱＳＡＲ。（１）ＰＣ＝３．００－２．７４ＣＱＳ－０．１５ＥＨＯＭＯ＋０．２２ＳＨＥＰ；（２）ＰＣ＝１０．０６－０．９６ＣＱＳ＋１．０７ＥＬＵＭＯ＋０．６６ＳＨＥＰ。结论：ＱＳＡＲ表明化合物抑制核苷酸还原酶的机制是络合机制。Purpose: To study the QSAR of the ribonucleotide reductase inhibitors on the electron level. Methods: By using the CNDO/2 quantum chemical method, 32 substituted hydroxamic acids, 5 substituted benzamides and 7 substituted methyl benzoates have been calculated. These 44 compounds were studied by step regression method. Results: Two quantitative structure-(ribonucleotide reductase inhibitors) activity relationships of two group (hydroxamic acids and benzamides, methyl benzoates) were botained. They were:(1)PC=3 00-2 74 CQS-0.15 EHOMO+0.22 SHEP for substituted hydroxamic acids and;(2)PC=10.06-0.96 CQS+1.07 ELU MO+0.66 SHEP for substituted benzamides and methyl benzoates. Conclusions: The quantum chemical indexes in the two QSAR affected the inhibitory activity to similar degree and the mechanism of inhibition of ribonucleotide reductase by inhibitors involves metal chelation. The inhibitory activities of the compounds may be predicated by the QSAR.

关 键 词：核苷酸还原酶 抑制剂 QSAR 抗癌药 

分 类 号：R979.11[医药卫生—药品] R962[医药卫生—药学]