Fini A, Roda A, Bellini A M, Mencini E, Guarneri M
Istituto di Scienze Chimiche, Bologna, Italy.
J Pharm Sci. 1990 Jul;79(7):603-5. doi: 10.1002/jps.2600790712.
Some representative physicochemical properties of benzylamido and amino derivatives of common bile acids have been determined and correlated with their antimicrobial activity against gram-positive bacterial strains. Steroid hydroxyls do not affect the basicity of amino derivatives; they promote solubility in a parallel way to unconjugated bile acids and mainly control hydrophobicity of this class of compounds as measured by log P values. Activity was correlated to hydrophobicity; that is, the nature of the side chain modulated activity, affected basicity, and facilitated changes in partition ability. Benzylamino derivatives proved to be even more active than the corresponding amides when ionization is taken into account. Trihydroxy derivatives possess the lowest log P values and were practically inactive. Decreased activity was also observed in those cases where, due to the orientation of the hydroxy group in the 6 or 7 position, the back beta face of the molecule had a reduced hydrophobic surface area. Antimicrobial activity, in terms of -log MIC (minimal inhibitory concentration), was found to correlate linearly with log P values of uncharged species. This linear relationship is discussed with respect to the structure of the steroid moiety and the ability of these molecules to cross cellular membranes.
已测定了常见胆汁酸的苄基酰胺和氨基衍生物的一些代表性物理化学性质，并将其与它们对革兰氏阳性细菌菌株的抗菌活性相关联。甾体羟基不影响氨基衍生物的碱性；它们以与未结合胆汁酸平行的方式促进溶解性，并主要通过log P值来控制这类化合物的疏水性。活性与疏水性相关；也就是说，侧链的性质调节活性、影响碱性，并促进分配能力的变化。当考虑离子化时，苄基氨基衍生物被证明比相应的酰胺更具活性。三羟基衍生物的log P值最低，实际上没有活性。在那些由于6或7位羟基的取向导致分子的背面β面疏水性表面积减小的情况下，也观察到活性降低。就-log MIC（最小抑菌浓度）而言，抗菌活性与不带电荷物种的log P值呈线性相关。针对甾体部分的结构以及这些分子穿过细胞膜的能力讨论了这种线性关系。
