37 ノゲイトウCelosia argenteaより単離した新規環状ペプチドcelogentin A-H,Jの構造とチューブリン重合阻害活性(口頭発表の部)

概要

論文の詳細を見る
Microtubules play a pivotal role in mitotic spindle assembly and cell division. These cytoskeletal elements are formed by the self-association of the αβ tubulin heterodimers. There are a number of natural compounds which inhibit the microtuble formation and the mitotic arrest of eucaryotic cells. The antimitotic agents have potential applications in drug development. During our search for bioactive compounds from medicinal plants, we have found that moroidin (10) obtained from the seeds of C. argentea (Amaranthaceae), which is a unique bicyclic peptide originally isolated from Laportea moroides (Labiatae), remarkably inhibits the tubulin polymerization. Further investigation of the extract of C. argentea resulted in the isolation of nine new moroidin-type bicyclic peptides, celogentins A-H and J (1-9). The structures and absolute stereochemistry were determined by using extensive NMR methods and chemical means. Celogentins A-H, and J (1-9) inhibited the polymerization of tubulin. and celogentin C (3) was 4 times more potent than moroidin (10) in the inhibitory activity. Celogentin C with the Pro residue in the right hand ring showed 30 times more potent activity than celogentin A (1), while moroidin (10), celogentins E (5), and F (6) with the Gly residue in the right hand ring showed 10 times more than celogentin A (1). Potency of celogentins G (7), H (8), and J (9) with Ile^4 residue was comparable to that of celogentins E (5) and F (6) with Val^4 residue. The presence of additional Lys^9 residue in celogentin B (2) seems not to influence severely the inhibitory activity. Structure-activity relationship study using moroidin derivatives (14-16) and analog (17) as well as celogentins A-H, and J (1-9) and moroidin (10) indicates that the ring size and conformations of the bicyclic peptides including unusual non-peptide connections among β^5-Leu, Trp, and His residues would be important for their biological activity.
天然有機化合物討論会の論文
2002-09-01

37 ノゲイトウCelosia argenteaより単離した新規環状ペプチドcelogentin A-H,Jの構造とチューブリン重合阻害活性(口頭発表の部)

スポンサーリンク

概要

著者

関連論文

スポンサーリンク