Problems that Can Occur when Assaying Extracts to Pure Compounds in Biological Systems.

For a significant number of years, scientists of many persuasions have assayed natural product materials ranging from crude extracts to pure compounds, in a multitude of assays causally related to some biological processes. However, in a very significant number of submitted papers and published articles, what may be considered as canned biological assays were used, and if a positive effect was observed, then the authors would claim that the material assayed was a potential drug lead. This also occurred with pure synthetic compounds and compounds derived from natural products by simple chemical modifications. However, what has now become quite obvious-with all such classes of materials-is that there are many promiscuous players with multiple bioactivities. These can range from relatively crude extracts, pure compounds from natural products, synthetic processes that produce natural product derivatives, and even compounds that are truly synthetic in origin. There is also a potential problem with the data from crude to purified extracts being used to claim some form of beneficial activities for such materials, to sell that particular mixture to the lay public, by very careful descriptions of its possible uses due to legal hurdles. With the advent of artificial intelligence and very large compound databases, some of which may well contain impure materials, scientists from a variety of backgrounds have begun to utilize such listings to obtain compounds for their low to high throughput biological screens, without realizing that there are very significant numbers of active compounds (eg, pan assay interference compounds and invalid metabolic panaceas), that will hit in many different screens for a variety of reasons, thus leading to significant wasted efforts and published scientific articles that have incorrect results. This commentary gives some of the history of such materials but is designed to be used as a warning to both researchers and in particular, journal editors, and reviewers, that reports of biological results that are claimed to be the result of the compounds used, need to be very carefully screened for results due to such promiscuous compounds, irrespective of their nominal source(s). All literature searches were made by the author and the background knowledge has come from more than 55 years of research in industry and governmental laboratories in both the United Kingdom and the United States, for enzyme inhibitors/activators as well as antimicrobial and antitumor lead compounds mainly from natural product sources. The conclusion that I came up with as a result is this: Caveat emptor. (