title: Absolute configuration and selective trypanocidal activity of gaudichaudianic acid enantiomers.
abstract: 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 showed a synergistic effect, with the racemic mixture being the most active.
authors.affiliation: Departamento de Química Orgânica, Instituto de Química, Universidade Estadual Paulista (UNESP), Araraquara, SP 14800-900, Brazil. joaombj@hotmail.com
authors.forename: João M
authors.initials: JM
authors.lastname: Batista
authors.forename: Andrea N L
authors.initials: AN
authors.lastname: Batista
authors.forename: Daniel
authors.initials: D
authors.lastname: Rinaldo
authors.forename: Wagner
authors.initials: W
authors.lastname: Vilegas
authors.forename: Daniela L
authors.initials: DL
authors.lastname: Ambrósio
authors.forename: Regina M B
authors.initials: RM
authors.lastname: Cicarelli
authors.forename: Vanderlan S
authors.initials: VS
authors.lastname: Bolzani
authors.forename: Massuo J
authors.initials: MJ
authors.lastname: Kato
authors.forename: Laurence A
authors.initials: LA
authors.lastname: Nafie
authors.forename: Silvia N
authors.initials: SN
authors.lastname: López
authors.forename: Maysa
authors.initials: M
authors.lastname: Furlan
mesh_terms: D001565:Benzoates / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D002851:Chromatography, High Pressure Liquid; D002942:Circular Dichroism; D015394:Molecular Structure; D031701:Piper / Q000737:chemistry*; D018515:Plant Leaves / Q000737:chemistry; D018517:Plant Roots / Q000737:chemistry; D018547:Plant Stems / Q000737:chemistry; D036226:Seedlings / Q000737:chemistry; D013237:Stereoisomerism; D014344:Trypanocidal Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D001565:Benzoates; D014344:Trypanocidal Agents; C494629:gaudichaudianic acid