Molecular diversity and natural products

Abstract

Natural products have long represented the mayor source ofdrugs,andeventodaytheyremainattheforefrontofpharma-ceutical research. Between 1982 and 2002, 28% of the NewChemicalEntities(NCE)approvedbytheFDAwerenaturalproducts or derivatives of natural products [1], a very highshare, since only less than 1% of the characterized organiccompounds are of natural origin. Natural products are stillplaying a major role in the realm of anti-cancer and anti-infectivedrugdiscovery,buttheirrelevanceinotherfieldshasconstantly declined in the wake of the introduction of “hun-gry” methodologies like combinatorial chemistry and ultra-high throughput screening. More recently, a resurgence isbeingwitnessed,owingtothegrowingawarenessthatnaturalproductsrepresentnotonlypotentialNewChemicalEntities(NCE), but also privileged structures to explore the chemi-cal space around a target. Plants, fungi, bacteria, and marineorganisms make medicinally interesting compound for rea-sonsoftheirown,thatnotnecessarilyoverlapwiththeneeds.Nevertheless, natural products are made by enzymes, andtheir shape must be complementary to that of a biologicalsurface. This makes them privileged structures in terms ofchemicalspaceofbiologicalrelevance.Naturalproductsare“sticky”towardbiologicalsurfacesnotonlyforthepresenceof functional groups capable to bind biomolecules throughthewholearsenalofnon-covalentinteraction(hydrogen-and