7-Diethylamino-3(2'-benzoxazolyl)-coumarin is a novel microtubule inhibitor with antimitotic activity in multidrug resistant cancer cells.
Microtubules are a proven target for anticancer drug development because they are critical for mitotic spindle formation and the separation of chromosomes at mitosis. We here report a novel synthetic microtubule inhibitor 7-diethylamino-3(2'-benzoxazolyl)-coumarin (DBC). DBC causes destabilization of microtubules, leading to a cell cycle arrest at G(2)/M stage. In addition, human cancer cells are more sensitive to DBC (IC(50) 44.8-475.2nM) than human normal fibroblast (IC(50) 7.9microM), and DBC induces apoptotic cell death of cancer cells. Furthermore, our data show that DBC is a poor substrate of drug efflux pumps and effective against multidrug resistant (MDR) cancer cells. Taken together, these results describe a novel pharmacological property of DBC as a microtubule inhibitor, which may make it an attractive new agent for treatment of MDR cancer.
KIST Gangneung Institute, Gangneung, Republic of Korea.
Su-Nam
SN
Kim
Nam Hyun
NH
Kim
Yeon Sook
YS
Park
Hanna
H
Kim
Seokjoon
S
Lee
Qian
Q
Wang
Yong Kee
YK
Kim
D049933:Aminocoumarins / Q000494:pharmacology* / Q000627:therapeutic use; D050256:Antimitotic Agents / Q000494:pharmacology / Q000627:therapeutic use; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001583:Benzoxazoles / Q000494:pharmacology* / Q000627:therapeutic use; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D003374:Coumarins / Q000494:pharmacology* / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm; D016195:G2 Phase / Q000187:drug effects; D006801:Humans; D020128:Inhibitory Concentration 50; D008870:Microtubules / Q000187:drug effects; D050257:Tubulin Modulators / Q000494:pharmacology* / Q000627:therapeutic use
C540953:7-diethylamino-3(2'-benzoxazolyl)coumarin; D049933:Aminocoumarins; D050256:Antimitotic Agents; D000970:Antineoplastic Agents; D001583:Benzoxazoles; D003374:Coumarins; D050257:Tubulin Modulators