Development of tubulin-polymerization inhibitors based on the thalidomide skeleton.
We synthesized a series of compounds based on the potent tubulin-polymerization inhibitor 5-hydroxy-2-(2,6-diisopropylphenyl)-1H-isoindole-1,3-dione [5HPP-33 (3)], which is structurally derived from thalidomide (1), and investigated their inhibitory effects on tubulin polymerization. Direct interaction between 5HPP-33 (3) and alpha,beta-tubulin heterodimer protein was demonstrated by means of a surface plasmon resonance study.
Aoyama
Hiroshi
H
Institute of Molecular & Cellular Biosciences, The University of Tokyo, Bunkyo-ku, Tokyo, Japan. aoyama@iam.u-tokyo.ac.jp
Noguchi
Tomomi
T
Misawa
Takashi
T
Nakamura
Takanori
T
Miyachi
Hiroyuki
H
Hashimoto
Yuichi
Y
Kobayashi
Hisayoshi
H
D001704:Biopolymers / Q000037:antagonists & inhibitors*; D019281:Dimerization; D009682:Magnetic Resonance Spectroscopy; D013792:Thalidomide / Q000737:chemistry*; D014404:Tubulin / Q000737:chemistry*
D001704:Biopolymers; D014404:Tubulin; D013792:Thalidomide