Résumé
Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest and induce apoptosis of tumor cells. A series of novel tetrahydro-beta-carboline derivatives were synthesized as kinesin spindle protein inhibitor and evaluated as potential antitumor agents. All compounds showed promising KSP inhibitiory activity. Compounds 8 and 9 exhibited better antitumor activity (Lung/A549, Stomach/AGS) than CK0106023 with GI50/IC50 values (1.07/1.62 and 1.46/3.27 micromol x L(-1), 1.09/>10 and 1.22/6.33 micromol x L(-1), respectively).
Sujets)
Humains , Antinéoplasiques , Chimie , Pharmacologie , Carbolines , Chimie , Pharmacologie , Lignée cellulaire tumorale , Prolifération cellulaire , Concentration inhibitrice 50 , Kinésine , Pharmacologie , Structure moléculaireRésumé
Kinesin spindle protein (KSP/Eg5) is essential for the formation and maintenance of bipolar spindles during mitosis. Inhibition of this protein leads to cell cycle arrest and apoptosis without interfering other microtubule-dependent processes. Therefore, it is a potential target in cancer therapy. Here, a series of tetrahydro-beta-carboline derivatives 5a - k were synthesized as kinesin spindle protein inhibitor. Their structures were confirmed with 1H NMR, ESI-MS and elemental analysis. The synthesized compounds were evaluated for their inhibition of KSP.