Absolute Configuration and Selective Trypanocidal Activity of Gaudichaudianic Acid Enantiomers

Gaudichaudianic acid, a prenylated chromene isolated from Piper gaudichaudianum, has been described as a potent trypanocidal compound against the Y-strain of Trypanosoma cruzi. We herein describe its isolation as a racemic mixture followed by enantiomeric resolution using chiral HPLC and determination of the absolute configuration of the enantiomers as (+)-S and (-)-R by means of a combination of electronic and vibrational circular dichroism using density functional theory calculations. Investigation of the EtOAc extract of the roots, stems, and leaves from both adult specimens and seedlings of P. gaudichaudianum revealed that gaudichaudianic acid is biosynthesized as a racemic mixture from the seedling stage onward. Moreover, gaudichaudianic acid was found exclusively in the roots of seedlings, while it is present in all organs of the adult plant. Trypanocidal assays indicated that the (+)-enantiomer was more active than its antipode. Interestingly, mixtures of enantiomers stowed a synergistic effect, with the racemic mixture being the most active.

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

State of Sao Paulo Research Foundation (FAPESP)[2003/02176-7]

State of Sao Paulo Research Foundation (FAPESP)[2008/58658-3]

Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)

The Brazilian Federal Agency for Support and Evaluation of Graduate Education (CAPES)[3686/09-4]

Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES)

National Council for Scientific and Technological Development (CNPq)

Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq)