Chemistry, pharmacological potential and molecular phylogeny of Croton (Euphorbiaceae), emphasis on native species

Abstract

Croton is one of the largest genera in Euphorbiaceae, with many species in the Brazilian flora. Many species are used in traditional medicine and several medicinal products derived from Croton species are traded internationally. The chemistry of the genus is widely diverse, including several classes of diterpenes, in addition to alkaloids, flavonoids, volatile oils, etc. The present project aims to widen the knowledge about the chemistry of Croton and the biological activities of its secondary metabolites, and also to test a hypothesis of preference of occurrence of alkaloids in the New World and to correlate the distribution of classes of compounds with phylogeny. Leaves and bark of about 30 species will be analyzed by gas chromatography/mass spectroscopy, aiming to establish the composition of diterpenes, alkaloids and volatile oils. Flavonoids will be extracted and identified by high pressure liquid chromatography and traditional methods of hydrolysis, glycoside and aglycone analysis by UV/visible and sugar identification. Focus will be concentrated on materials with higher contents of certain metabolites, particularly new compounds or those which have not yet been object of pharmacological evaluation. These compounds will be isolated using preparative liquid chromatography. Structure determination will be carried out in case new compounds are isolated. For isolated compounds tests will be carried out of antioxidant activity, by the DPPH and -carotene/linoleic acid methods, antimicrobial activity (Bacillus subtilis, Enterococcus faecalis, Escherichia coli, Klebsiella pneumoniae, Proteus mirabilis, Pseudomonas aeruginosa, Salmonella typhimurium, Staphylococcus aureus e Candida albicans) and antiproleferative activity (human tumor cells of lymphoid leukemia (K-562), melanoma (UACC-62), lung (NCI-ADR) colon (HT-29), ovary (OVCAR-3), kidney (786-0) and prostate (PC-3)). From species not present in the available phylogeny of Croton, DNA will be extracted and the regions ITS and trnL-trnF sequenced aiming inclusion of the species in the phylogeny. The distribution and evolution of secondary metabolites in Croton will be evaluated using the McClade software. (AU)