Natural chromenes and chromene derivatives as potential anti-trypanosomal agents.
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.
Batista
João Marcos
JM
Instituto de Química, Universidade Estadual Paulista, Prof. Francisco Degni, 14801-970, Araraquara, SP, Brazil.
Lopes
Adriana Aparecida
AA
Ambrósio
Daniela Luz
DL
Regasini
Luis Octávio
LO
Kato
Massuo Jorge
MJ
Bolzani
Vanderlan da Silva
Vda S
Cicarelli
Regina Maria Barretto
RM
Furlan
Maysa
M
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*
D001578:Benzopyrans; D014344:Trypanocidal Agents