RESUMO
Three new bicyclic peptides, celogentins A (1), B (2), and C (3), have been isolated together with a known-related peptide, moroidin (4), from the seeds of Celosia argentea, and their structures including absolute stereochemistry were determined by using extensive NMR methods and chemical means. Celogentins A (1), B (2), and C (3) inhibited the polymerization of tubulin, and celogentin C (3) was four times more potent than moroidin (4) in the inhibitory activity. Structure-activity relationship study using moroidin derivatives 5-7 and analogue 8 as well as celogentins A-C (1-3) and moroidin (4) indicates that the bicyclic ring system including unusual non-peptide connections among beta(s)-Leu, Trp, and His residues characteristic of celogentins and moroidin, with ring size and conformations suitable for interaction with tubulin would be important for their biological activity.
Assuntos
Antineoplásicos/isolamento & purificação , Magnoliopsida/química , Proteínas dos Microtúbulos , Peptídeos Cíclicos/isolamento & purificação , Peptídeos Cíclicos/farmacologia , Plantas Medicinais/química , Sementes/química , Animais , Antineoplásicos/química , Antineoplásicos/farmacologia , Encéfalo , Proteínas dos Microtúbulos/efeitos dos fármacos , Microtúbulos/efeitos dos fármacos , Estrutura Molecular , Ressonância Magnética Nuclear Biomolecular , Peptídeos Cíclicos/química , SuínosRESUMO
A unique bicyclic peptide, moroidin (1), from the seeds of Celosia argentea (Amaranthaceae) strongly inhibited the polymerization of tubulin. The stereostructure of moroidin (1) was reinvestigated by spectroscopic data, chemical degradation, and molecular dynamics simulation.