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 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.
Kobayashi
J
J
Graduate School of Pharmaceutical Sciences, Hokkaido University, Sapporo 060-0812, Japan. jkobay@pharm.hokudai.ac.jp
Suzuki
H
H
Shimbo
K
K
Takeya
K
K
Morita
H
H
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D001921:Brain; D019684:Magnoliopsida / Q000737:chemistry*; D008868:Microtubule Proteins / Q000187:drug effects; D008870:Microtubules / Q000187:drug effects; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010456:Peptides, Cyclic / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D010946:Plants, Medicinal / Q000737:chemistry*; D012639:Seeds / Q000737:chemistry*; D013552:Swine
D000970:Antineoplastic Agents; D008868:Microtubule Proteins; D010456:Peptides, Cyclic; C445727:celogentin A; C445726:celogentin B; C445725:celogentin C