Unconventional natural sources for future drug discovery.

Natural products used as food or drinks, clues from the fascinating science of zoopharmacognosy, terrestrial animals and their excreta, and many other NPs not primarily known for their medical use, seem to have, to a great extent, escaped the attention of natural product research. It is nevertheless highly probable that these sources could contain biologically active compounds, some of which will prove to be valuable lead candidates for novel drugs. Natural products have been the most successful source of drugs ever [1,2]. Historically, the most important natural sources have been plants. Research progressed along two major lines: ethnopharmacology (medicinal herbs, substances of abuse, ordeal poisons) and toxicology (poisonous plants, venomous animals, arrow and fish poisons) [3]. These strategies have produced many valuable drugs and are likely to continue to produce lead compounds [4]. It must be stated that traditional medicines have not been found by systematic research but by a combination of coincidence and observation, and at best by trial and error. Until the beginning of the 20th century, knowledge about receptors, bacteria and viruses was virtually nil [5]. As a consequence, many valuable natural compounds have escaped discovery. Due to the inability to diagnose disease accurately in ancient times, it is unlikely that in depth investigations of, for example, traditional Chinese Medicine and Ayurveda will directly lead to treatments for life-threatening diseases, although this can not be excluded. Fleming’s serendipitous discovery of penicillin was the start of the exploration of the second most investigated and, consequently, the second most prolific natural source: fungi. From those organisms, breakthroughs in the area of antibiotics, immunosuppressants and anticancer drugs have been realized. More recently, there has been a trend to explore marine environments. Already this has resulted in several marketed drugs and more are currently in clinical trials. Research on marine organisms has been the subject of several excellent reviews [6–10]. Ethnopharmacological, microbiological and marine sources must not be regarded as exhausted. The intention of this paper is to draw attention to other, unconventional sources that have never been investigated systematically in pharmacological assays. The first and most important step in drug discovery is the finding of leads. To facilitate that process, there are now a great variety of mechanismbased HTS assays. Traditionally, the natural sources investigated were well-determined individual species: mostly plants and fungi. Many of the sources discussed here are different: they are not individual species, and botanical or zoological identification in some cases is impossible.