title: Preparation and antitrypanosomal activity of secochiliolide acid derivatives.
abstract: Secochiliolide acid (1) isolated from the Patagonian shrub Nardophyllum bryoides, was used as a scaffold for the preparation of a series of nine derivatives. Compound 1 and its derivatives were tested against Trypanosoma cruzi epimastigotes grown in liquid media. It was first observed that secochiliolide acid (1) inhibited the proliferation of the parasites, with an IC50 of 2 μg/mL. Six of the synthesized derivatives were also active with IC50's between 2 and 7 μg/mL which are comparable to that of the commercial drug benznidazole (2.5 μg/mL). These results indicate that the carboxyl group is not essential for the bioactivity of 1, while the presence of the tetrasubstituted exocyclic double bond seems to be important. Moreover, the presence of the furan and spirolactone rings is not essential for the bioactivity per se, but is important in combination with other structural fragments present in the molecule.
authors.affiliation: UMYMFOR-CONICET - Departamento de Química Orgánica, Facultad de Ciencias Exactas y Naturales, Universidad de Buenos Aires, Ciudad Universitaria, Pab 2 1428, Buenos Aires, Argentina.
authors.forename: Gastón E
authors.initials: GE
authors.lastname: Siless
authors.forename: Esteban
authors.initials: E
authors.lastname: Lozano
authors.forename: Marianela
authors.initials: M
authors.lastname: Sánchez
authors.forename: Marcia
authors.initials: M
authors.lastname: Mazzuca
authors.forename: Miguel A
authors.initials: MA
authors.lastname: Sosa
authors.forename: Jorge A
authors.initials: JA
authors.lastname: Palermo
mesh_terms: D019659:Asteraceae / Q000737:chemistry; D014355:Chagas Disease / Q000188:drug therapy; D004224:Diterpenes / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D011422:Propionates / Q000737:chemistry* / Q000494:pharmacology*; D014344:Trypanocidal Agents / Q000737:chemistry* / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects* / Q000254:growth & development
chemical_list: D004224:Diterpenes; D011422:Propionates; D014344:Trypanocidal Agents; C587785:secochiliolide acid
keywords: Nardophyllum bryoides; Secochiliolide acid; Trypanosoma cruzi; trypanocidal activity