ESTIMATING THE LIPOPHILICITY OF NATURAL PRODUCTS USING A POLYMERIC REVERSED PHASE HPLC METHOD

The integration of physicochemical profiling screens such as LogP 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 logP values for a diverse set of commercially available drugs using the PRP-1 column. The logP 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 logP values. Some discrepancies were observed between the measured value of logP 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.