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

Abstract

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.

Keywords:

• drug discovery
• lipophilicity
• natural products
• polystyrene-divinylbenzene
• reversed-phase HPLC

ACKNOWLEDGMENTS

We thank Prasoon Gupta, Upasana Sharma, and Maia Mukherjee for the isolation of the marine natural products used in this study. The compounds were isolated for the molecular libraries screening network (MLSCN) funded by NIH grant P41GM07957. We also thank J. Haky for helpful discussions.