NOVEL HYDROPHOBIC INDEX FOR LFER OF ANTITUMOR AGENTS

本研究的目的是开发高性能液体的用途 用于物理化学测量的层析法 生物物质，特别是抗癌药物。的主旨是 该项目是建立药物及其疏水性的标准。 从反相中获得的适当保留数据得到的结构元素 在广泛的条件下进行层析，就组成 水有机元素是值得关注的。建议的疏水指数是基于 我们发现的支配保留的线性自由能关系(LFER) 在使用非极性固定相的液相色谱系统中。在……里面 反过来，结果将被用来建立生物反应和 药物的物理化学性质。为了建立药物受体的模型 相互作用，具有不同表面几何结构的非极性固定相 将被采用，并将尝试获得对 捆绑过程。将采用高效液相色谱(Hplc)进行简便、准确的检测。 测定pKa值、溶解度和辛醇-水分配的方法 使用微量物质的药物系数不需要 纯洁一点。保留数据与上述分子参数一起将是 用来尝试开发一种简单的层析方法来 药物在溶液中构象的定量研究及评价 选定抗癌药物的结合和转运特性。

The objective of this study is to develop the use of high performance liquid chromatography for physico-chemical measurements concerning the properties of biological substances, particularly the anti-cancer drugs. The main thrust of the project is the establishment of a hydrophobicity scale for drugs and their structural elements from appropriate retention data obtained in reversed phase chromatography over a wide range of conditions as far as the composition of the hydro-organic elements is concerned. The proposed hydrophobic index is based on linear free energy relationships (LFER) which we have found to govern retention in liquid chromatographic systems employing non-polar stationary phases. In turn, results will be used to develop LFER between biological response and physico-chemical properties of drugs. In order to model drug-receptor interactions, non-polar stationary phases having different surface geometries will be employed and an attempt will be made to gain quantitative insight into the binding process. HPLC will be employed to develop simple and accurate methods to measure pKa values, solubilities and octanol-water partition coefficients of drugs using minute quantities of material which do not have to be pure. Retention data together with the above molecular parameters will be used to attempt the development of a simple chromatographic approach to a quantitative study of drug conformation in solution as well as to evaluate binding and transport properties of selected anti-cancer drugs.