title: Natural chromenes and chromene derivatives as potential anti-trypanosomal agents.
abstract: The aim of the study was to investigate the anti-trypanocidal activities of natural chromene and chromene derivatives. Five chromenes were isolated from Piper gaudichaudianum and P. aduncum, and a further seven derivatives were prepared using standard reduction, methylation and acetylation procedures. These compounds were assayed in vitro against epimastigote forms of Trypanosoma cruzi, the causative agent of Chagas disease. The results showed that the most of the compounds, especially those possessing electron-donating groups as substituents on the aromatic ring, showed potent trypanocidal activity. The most active compound, [(2S)-methyl-2-methyl-8-(3''-methylbut-2''-enyl)-2-(4'-methylpent-3'-enyl)-2H-chromene-6-carboxylate], was almost four times more potent than benznidazole (the positive control) and showed an IC50 of 2.82 microM. The results reveal that chromenes exhibit significant anti-trypanocidal activities and indicate that this class of natural product should be considered further in the development of new and more potent drugs for use in the treatment of Chagas disease.
authors.affiliation: Instituto de Química, Universidade Estadual Paulista, Prof. Francisco Degni, 14801-970, Araraquara, SP, Brazil.
authors.forename: João Marcos
authors.initials: JM
authors.lastname: Batista
authors.forename: Adriana Aparecida
authors.initials: AA
authors.lastname: Lopes
authors.forename: Daniela Luz
authors.initials: DL
authors.lastname: Ambrósio
authors.forename: Luis Octávio
authors.initials: LO
authors.lastname: Regasini
authors.forename: Massuo Jorge
authors.initials: MJ
authors.lastname: Kato
authors.forename: Vanderlan da Silva
authors.initials: Vda S
authors.lastname: Bolzani
authors.forename: Regina Maria Barretto
authors.initials: RM
authors.lastname: Cicarelli
authors.forename: Maysa
authors.initials: M
authors.lastname: Furlan
mesh_terms: D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D021261:Parasitic Sensitivity Tests; D031701:Piper / Q000737:chemistry*; D013329:Structure-Activity Relationship; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000302:isolation & purification / Q000494:pharmacology*; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D001578:Benzopyrans; D014344:Trypanocidal Agents