Impuls Lecture – Looking for plant bioactive compound target: uno, nessuno o centomila

Plant metabolites are a very broad and heterogeneous set of intrinsically (bio)active compounds. Most of the interest towards these molecules depends on their possible use for human well-being – physical, psychic or aesthetic -, but it is important to remember that they have been selected from million-years-long evolution processes to permit plants surviving, growing and reproduction. Although natural products have not been developed to bind to human proteins, some of them can do it efficiently. There are at last two main theories to explain this phenomenon: the co-evolution [1] and the xenohormesis [2] theory. On these basis it is evident that a deep understanding of the mechanism of action of natural bioactive compounds is a very ambitious aim for researchers working in different scientific fields. Unfortunately, the actual targets of many plant metabolites are completely unknown; besides, there are a number of data demonstrating that most of these compounds can interact with several partners. However, the identification of the molecular target of a bioactive molecule has several advantages. For example, in the case of compounds used for human health, it allows to set up target-based assays and to allow structure activity relationships (SAR) studies to guide medicinal chemistry efforts towards lead optimization. Moreover, the knowledge of drug targets can also facilitate the identification of potential toxicities or side effects, if there is any precedent of toxicities for the identified target [3]. Achieving this in an effective, unbiased and efficient manner subsists as a significant challenge for the new era in drug discovery and optimization, plant science and evolutionary studies.

Keywords: Target identification, mechanism of action, bioactive compounds.

References:

[1] Ji HF, Li XJ, Zhang HY. Natural products and drug discovery. Can thousands of years of ancient medical knowledge lead us to new and powerful drug combinations in the fight against cancer and dementia? EMBO RepMar 2009; 10: 194 – 200

[2] Konrad TH, David AS. Xenohormesis: sensing the chemical cues of other species. Cell 2008; 133: 387 – 391

[3] Rix U, Superti-Furga G. Target profiling of small molecules by chemical proteomics. Nat Chem Biol 2009; 5: 616 – 624

No conflict of interest has been declared by the author(s).