Lasslo A, Dillingham E O, McCastlain J C, Carter-Burks G, Quintana R P, Johnson R W, Naylor J L
Med Prog Technol. 1986;11(3):109-21.
Striking relationships were observed, in vitro, between the molecular constitution of synthetic entities, their aggregation-inhibitory potency (as determined in ADP-induced human blood platelet aggregation), and their cellular toxicity (as assessed by their inhibition of cultured mouse fibroblast L-cell growth). Effects exerted on platelets tended to reflect interactions between the molecules' aggregation-inhibitory specific functions and the platelets' corresponding target sites, while fibroblasts were generally more susceptible to the molecular constitution's hydrophobic character. The hyperbolic relationships between concentrations effecting 50% inhibition and slopes of concentration-response curves reflect net activity from both specific and nonspecific receptor site interactions, with the latter being dominant, and indicated that the assays approximated equilibrium systems. Plotting logarithm values of concentrations effecting 50% inhibition against logarithms of reciprocal slopes for concentration response curves yielded multiple regression coefficients of R = 0.97 (platelet aggregation-inhibitory potency) and R = 0.98 (fibroblast growth-inhibitory potency).
在体外实验中，观察到合成实体的分子组成、它们的聚集抑制效力（通过ADP诱导的人血小板聚集测定）以及它们的细胞毒性（通过对培养的小鼠成纤维细胞L-细胞生长的抑制评估）之间存在显著关系。对血小板产生的作用往往反映了分子聚集抑制特定功能与血小板相应靶位点之间的相互作用，而成纤维细胞通常对分子组成的疏水特性更敏感。影响50%抑制的浓度与浓度-反应曲线斜率之间的双曲线关系反映了特异性和非特异性受体位点相互作用的净活性，其中后者占主导地位，并表明这些测定近似于平衡系统。绘制影响50%抑制的浓度对数值与浓度反应曲线倒数斜率对数值的关系图，得到血小板聚集抑制效力的复相关系数R = 0.97和成纤维细胞生长抑制效力的复相关系数R = 0.98。
