NOVEL HYDROPHOBIC INDEX FOR LFER OF ANTITUMOR AGENTS

本研究的目的是开发使用高性能液体 色谱法，用于物理化学测量， 生物物质，特别是抗癌药物。 的主旨 该项目是建立一个疏水性规模的药物及其 从反相色谱中获得的适当保留数据中的结构元素 色谱法在广泛的条件下，只要组成的 水有机元素。 建议的疏水指数是基于 线性自由能关系（LFER），我们已经发现，管理保留 在使用非极性固定相的液相色谱系统中。 在 反过来，结果将用于开发生物反应和 药物的物理化学性质。 为了模拟药物受体 相互作用，具有不同表面几何形状的非极性固定相 将被雇用，并试图获得定量的洞察力， 绑定过程。 采用高效液相色谱法， 测定pKa值、溶解度和辛醇-水分配的方法 使用微量材料的药物系数， 要纯洁 保留数据与上述分子参数一起， 用于尝试开发一种简单的色谱方法， 药物在溶液中构象的定量研究以及评价 所选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.