Zheng Bo, West Lyndon M
Department of Pharmaceutical and Biomedical Sciences, The University of Georgia, Athens GA 30602-2352, USA.
J Liq Chromatogr Relat Technol. 2009;33(1):118-132. doi: 10.1080/10826070903430464. Epub 2009 Dec 11.
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.
将诸如Log P等物理化学分析筛选方法整合到天然产物药物发现计划中，正逐渐成为一种在高通量筛选前赋予天然产物库类药物性质的方法。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，以评估海洋天然产物的亲脂性。使用PRP-1柱对一系列市售药物进行实验测定的结果与文献中的Log P值之间发现了良好的相关性。使用新方法评估了一系列24种海洋天然产物的Log P，实验测定值与软件计算的Log P值之间观察到良好的相关性。对于含卤素原子的天然产物，Log P测量值与软件计算值之间存在一些差异。该方法快速、对杂质不敏感，所需化合物极少，适合整合到天然产物药物发现研究计划中。
