Will Natural Chemistry Diversity from Tropical Biodiversity Continue to Inspire Medicinal Chemistry?
Vanderlan da Silva Bolzani
São Paulo State University, Institute of Chemistry, Nuclei of Bioassays
Biosynthesis and Ecophysiology of Natural Products (NuBBE)
Araraquara, SP- Brazil
Abstract:
Certainly, the use of natural products has been the single most successful strategy in the discovery of novel medicines. Secondary metabolites from terrestrial and marine organisms have extensive past and present use in the treatment of many diseases, and have served as lead molecules both in their natural form and as templates for synthetic modification and total synthesis. Over ca. of 35 new drugs launched on the market between 2000 and 2009, originating from terrestrial plants, terrestrial microorganisms, marine organisms, and terrestrial vertebrates and invertebrates, are described, showing that natural chemical diversity continue to inspire drug discovery research. Together with several other natural products or their analogs undergoing clinical trials, natural products reinforce its importance in modern drug discovery. Thus, biodiversity, and in special plant species of Brazilian biomes, have a long history of use in the treatment of human diseases being a powerful source of new bioactive compounds of interest for Medicinal Chemistry. A well-known Amazonian species, (+)-tubocurarine (Chondrodendron tomentosum), known as curare, is an important example of traditional plants, which inspired the development of a new class of synthetic anesthetic drugs. In 1970, a Brazilian scientist, Sergio Ferreira discovered a peptide in the viper (Bothrops jararaca) venom, which was associated to the conversion of angiotensin I to angiotensin II during its passage through the pulmonary circulation. Later, this discovered resulted in Captopril (Capoten®), developed from this peptide after revolutionary concept of structure-based drug design, associated to QSAR-based modification on the terminal sulfhydryl moiety of the peptide, which provided a high potency of ACE inhibition (Bristol-Myers Squibb). Recently, our research on (-)-spectaline, a piperidine alkaloid isolated from Senna spectabilis has been used as start material for obtaining semi-synthetic derivatives, which are acetyl cholinesterase inhibitors (pre-clinical trials) demonstrating the importance of secondary metabolites isolated from our biodiversity. [FAPESP, Biota-FAPESP, CNPq, CAPES, APSEN].
