title: Semisynthesis of new aphidicolin derivatives with high activity against Trypanosoma cruzi.
abstract: Chagas disease continues to be a difficult disease to eradicate, largely because of the widespread populations it affects as well as the highly toxic effects of current therapies. Thus, the exploration of innovative scaffolds, ideally with distinct mechanisms of action, is urgently needed. The natural product aphidicolin and its effects on cell cycle division have been widely studied; it is a potent inhibitor of parasitic cells. In the present study, we report for the first time the semisynthesis of a series of aphidicolin derivatives, their unique structural features, and demonstration of their activity against Trypanosoma cruzi cells. Two demonstrated high potency and selectivity against parasitic amastigote cells, and thus show promise as new leads for Chagas disease treatment.
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Gabriela B
authors.initials: GB
authors.lastname: Santos
authors.affiliation: Laboratório de Química Medicinal e Computacional, Universidade de São Paulo, 13560-590 São Carlos, SP, Brazil.
authors.forename: Renata
authors.initials: R
authors.lastname: Krogh
authors.affiliation: Laboratório de Química Medicinal e Computacional, Universidade de São Paulo, 13560-590 São Carlos, SP, Brazil.
authors.forename: Luma G
authors.initials: LG
authors.lastname: Magalhaes
authors.affiliation: Laboratório de Química Medicinal e Computacional, Universidade de São Paulo, 13560-590 São Carlos, SP, Brazil.
authors.forename: Adriano D
authors.initials: AD
authors.lastname: Andricopulo
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Mônica T
authors.initials: MT
authors.lastname: Pupo
authors.affiliation: Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, 14040-903 Ribeirão Preto, SP, Brazil.
authors.forename: Flavio S
authors.initials: FS
authors.lastname: Emery
mesh_terms: D016590:Aphidicolin / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D014355:Chagas Disease / Q000188:drug therapy; D006801:Humans; D021261:Parasitic Sensitivity Tests; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000494:pharmacology / Q000627:therapeutic use; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D014344:Trypanocidal Agents; D016590:Aphidicolin
keywords: Aphidicolin; Chagas disease; Semisynthesis; T. cruzi; Terpenes