Discovery of tetrahydro-beta-carbolines as inhibitors of the mitotic kinesin KSP.
Inhibitors of kinesin spindle protein (KSP) are a promising class of anticancer agents that cause mitotic arrest in cells from a failure to form functional bipolar mitotic spindles. Here, we report the synthesis and biological evaluation of a novel series of tetrahydro-beta-carboline analogs based on the structure of the known KSP inhibitor HR22C16. Preferred compounds 11b, 12a and 19b were identified as potent inhibitors in a KSP ATPase assay with good anti-proliferative activity in A549 cells.
Jiangsu Key Laboratory of Carcinogenesis and Intervention, China Pharmaceutical University, Tongjiaxiang, Nanjing 210009, China.
Fei
F
Liu
Li-Qin
LQ
Yu
Cheng
C
Jiang
Lei
L
Yang
Wu-Tong
WT
Wu
Qi-Dong
QD
You
D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology; D002243:Carbolines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D045744:Cell Line, Tumor; D055808:Drug Discovery; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000737:chemistry* / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000737:chemistry / Q000494:pharmacology; D016547:Kinesins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D010636:Phenols / Q000737:chemistry / Q000494:pharmacology; D008941:Spindle Apparatus / Q000201:enzymology*
C552748:1-(3-hydroxyphenyl)-2-(4-aminobenzoyl)-6-chloro-1,2,3,4-tetrahydro-beta-carboline; C552747:1-(3-hydroxyphenyl)-2-(beta-aminopropionyl)-8-chloro-1,2,3,4-tetrahydro-beta-carboline; C552749:6-methyl-1-(indol-3-yl)-2-butyryl-1,2,3,4-tetrahydro-beta-carboline; D000970:Antineoplastic Agents; D002243:Carbolines; D004791:Enzyme Inhibitors; C483533:HR22C16; D007211:Indoles; D010636:Phenols; D016547:Kinesins