Sestili P, Spadoni G, Balsamini C, Scovassi I, Cattabeni F, Duranti E, Cantoni O, Higgins D, Thomson C
Istituto di Farmacologia e Farmacognosia, Università di Urbino, Italy.
J Cancer Res Clin Oncol. 1990;116(6):615-22. doi: 10.1007/BF01637083.
The purpose of this study was to examine the structure/activity relationships of a series of substituted benzamides as poly(ADP-ribose) polymerase inhibitors. The experimental approach has involved the use of in vitro and in vivo assays in order to gather information either on the intrinsic activity of the benzamides or on the effect of various pharmacodynamic parameters on the activity in vivo. Although some discrepancies between the data obtained in vivo and in vitro were found in this study, results seem to indicate that most powerful inhibitors were characterized by acylation of the -NH2 function in the 3 position or by substitution in this same position with hydroxy or methoxy groups. The best inhibitors were not cytotoxic under these experimental conditions. Computed calculations of molecular electrostatic potential of these molecules were also performed and a good correlation was found between the similarity index and the experimental inhibitory activity.
本研究的目的是考察一系列取代苯甲酰胺作为聚（ADP - 核糖）聚合酶抑制剂的构效关系。实验方法包括使用体外和体内试验，以便收集有关苯甲酰胺的内在活性或各种药效学参数对体内活性影响的信息。尽管本研究发现体内和体外获得的数据存在一些差异，但结果似乎表明，最有效的抑制剂的特征是在3位的 -NH2官能团被酰化，或在同一位置被羟基或甲氧基取代。在这些实验条件下，最佳抑制剂没有细胞毒性。还对这些分子的分子静电势进行了计算，发现相似性指数与实验抑制活性之间具有良好的相关性。
