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Eur J Med Chem. 2013;70:427-33. doi: 10.1016/j.ejmech.2013.09.042. Epub 2013 Oct 2.

Synthesis, biological evaluation and molecular docking studies of flavone and isoflavone derivatives as a novel class of KSP (kinesin spindle protein) inhibitors.

Author information

1
State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.

Abstract

The kinesin spindle protein (KSP) is involved in the formation of bipolar mitotic spindle during cell division and it becomes a new target to overcome the neurotoxicity of MTs inhibitors. A series of flavone and isoflavone derivatives (1a-7c) have been designed, synthesized and evaluated as potential KSP inhibitors. Among them, 2c displayed the most potent inhibitory activity in vitro, which inhibited the growth of MCF-7 and Hela cell lines with IC50 values of 4.8 and 4.3 μM, respectively, and also exhibited significant KSP inhibitory activity (IC₅₀ = 0.023 μM). The new compounds can induce irregular monoastral spindles, the characteristic phenotype for KSP inhibiting agents. Docking simulation was further performed to determine the probable binding model.

KEYWORDS:

Antimitotic; Flavone; Isoflavone; KSP; Kinesin inhibitor; Monoastral spindles

PMID:
24184776
DOI:
10.1016/j.ejmech.2013.09.042
[Indexed for MEDLINE]

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