Celogentins A−C, New Antimitotic Bicyclic Peptides from the Seeds of Celosia argentea

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 β^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.