In:
ChemMedChem, Wiley, Vol. 12, No. 5 ( 2017-03-07), p. 399-406
Abstract:
The biological importance of microtubules in mitosis makes them an interesting target for the development of anticancer agents. In this study, a series of novel chalcone‐containing shikonin derivatives was designed, synthesized, and evaluated for biological activities. Among them, derivative PMMB‐259 [( R )‐1‐(5,8‐dihydroxy‐1,4‐dioxo‐1,4‐dihydronaphthalen‐2‐yl)‐4‐methylpent‐3‐en‐1‐yl ( E )‐2‐(4‐(3‐oxo‐3‐(3‐(trifluoromethoxy)phenyl)prop‐1‐en‐1‐yl)phenoxy)acetate] was identified as a potent inhibitor of tubulin polymerization. Further investigation confirmed that PMMB‐259 can induce MCF‐7 cell apoptosis, reduce the mitochondrial transmembrane potential, and arrest the cell cycle at the G 2 /M phase. Moreover, the morphological variation of treated cells was visualized by confocal microscopy. The results, along with docking simulations, further indicated that PMMB‐259 can bind well to tubulin at the colchicine site. Overall, these studies may provide a new molecular scaffold for the further development of antitumor agents that target tubulin.
Type of Medium:
Online Resource
ISSN:
1860-7179
,
1860-7187
DOI:
10.1002/cmdc.201700001
Language:
English
Publisher:
Wiley
Publication Date:
2017
detail.hit.zdb_id:
2209649-8
SSG:
15,3
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