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A recent article by Baell(1) on the problems experienced by medicinal chemists with pan-assay interference compounds (PAINS) and Shoichet’s work(2) on the impact of aggregation occurring in high throughput screening libraries, prompts a consideration of how these and other similar problems are experienced by pharmacognosists with promiscuous invalid metabolites as panaceas (PIMPs). Contrary to the classical definition of secondary metabolites as being species specific (or near specific), several natural products, particularly in the more extensively investigated plant kingdom, are common across species, genera, and even families (e.g. β-sitosterol). In the course of bioactivity-guided fractionation, PIMPs have shown up as major components in active fractions of a wide variety of pharmacological assays, i.e., they have been designated as panaceas. As in the case of PAINS, these assay results are almost invariably invalid and lead enthusiastic young scientists down a garden path. Why does this happen and how can it be avoided? Interestingly, the advances in modern methods of structure determination have exacerbated this problem, because it is possible to determine the structure of a compound when it is quite impure, and residual complexity is characteristic of chromatographic fractionation. That these residuals are often the source of the bioactivity is also frequently overlooked. Classic examples where this has occurred and ways to avoid it will be outlined.

1. Baell. Med. Chem.Lett.2015,6,229.
2. Seidler,McGovern,Doman,Shoichet. J.Med.Chem.2003,46,4477.