The integration of physicochemical profiling screens such as Log P into natural products drug discovery programs is emerging as an approach to front-load drug-like properties of natural product libraries for high-throughput screening. In this study a fast-gradient HPLC method using a polystyrene-divinylbenzene PRP-1 column was developed to estimate the lipophilicity of marine natural products. An excellent correlation was found between the results of the experimental determined and the literature log P values for a diverse set of commercially available drugs using the PRP-1 column. The log P of a series of 24 marine natural products were evaluated using the new method and a good correlation was observed between the experimentally determined and software calculated log P values. Some discrepancies were observed between the measured value of log P and the software calculations of the natural products containing halogens atoms. The method is rapid, insensitive to impurities, and requires very little compound and is amenable for integration into a natural products drug discovery research program.

中文翻译：

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使用聚合反相 HPLC 方法估计天然产物的亲脂性

将诸如 Log P 之类的物理化学分析筛选整合到天然产物药物发现计划中，正在成为一种用于高通量筛选的天然产物库的前载类药物特性的方法。在本研究中，开发了一种使用聚苯乙烯-二乙烯基苯 PRP-1 柱的快速梯度 HPLC 方法来估计海洋天然产物的亲油性。使用 PRP-1 色谱柱，在确定的实验结果与多种市售药物的文献 log P 值之间发现了极好的相关性。使用新方法对一系列 24 种海洋天然产品的 log P 进行了评估，并且在实验确定的 log P 值与软件计算的 log P 值之间观察到了良好的相关性。log P 的测量值与含有卤素原子的天然产物的软件计算值之间存在一些差异。该方法快速，对杂质不敏感，需要的化合物很少，适合整合到天然产物药物发现研究计划中。