Bioprospecting Program-BIOTA: A Rational Search for Drug Discovery from Brazilian Biodiversity

Certainly, the use of natural products has been the single most successful strategy in the discovery of novel medicines, and their importance is evidenced by the new chemical entities (NCE) approved by regulatory authorities around the world in the past decade. The biodiversity found in Brazil makes it a very feasible source of biological active compounds and its preservation is an important goal both for the intrinsic value of this enormous biological resource, and for its huge potential as a source of new drugs. Our collaborative project at Biota-FAPESP has identified antifungal, anticancer, antimalarial and acetylcholinesterase inhibitor compounds from plant species of Cerrado and Atlantic Forest. Among the isolates, the xanthones mangiferin (IC₅₀=32,55µM), muraxanthone (IC₅₀ 56.72µM), 2-(2'-O-trans-caffeoyl)-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (IC₅₀ 61.88µM), 2-(2'-O-trans-cinnamoyl)-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (IC₅₀=46.31µM), 2-(2'-O-trans-coumaroyl)-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (IC₅₀ 55.94µM), 2-(2'-O-benzoyl)-C-β-D-glucopyranosyl-1,3,6,7-tetrahydroxyxanthone (IC₅₀ 55.94µM) and muraxanthone (IC₅₀ 56.72µM) showed antimalarial activity, using chroroquine as positive control. As acetylcholinesterase inhibitors, piperidine alkaloid acetyl-spectaline (IC₅₀=24.80µM) and their derivatives (2R,3R,6S)-2-methyl-6-(13-oxotetradecyl)piperidin-3-yl acetate hydrochloride (IC₅₀=7.32µM) and tert-butyl (2R,3R,6S)-20methyl-6-(13-oxotetradecyl)-piperidin-3-yl carbamate hydrochlride (IC₅₀=15.10µM) have been considered lead molecules for Alzheimer disease when compared with standard control: galanthamine (IC₅₀=3.10µM).