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Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death

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Title Synthesis of microtubule-interfering halogenated noscapine analogs that perturb mitosis in cancer cells followed by cell death
 
Creator ANEJA, RITU
VANGAPANDU, SURYA N
LOPUS, MANU
VISWESARAPP, VIJAYA G
DHIMAN, NEERUPMA
VERMA, AKHILESH
CHANDRA, RAMESH
PANDA, DULAL
JOSHI, HARISH C
 
Subject cell cycle
mitotic arrest
anticancer
tubulin-binding
 
Description We have previously identified the naturally occurring non-toxic antitussive phthalideisoquinoline alkaloid, noscapine as a tubulin-binding agent that arrests mitosis and induces apoptosis. Here we present high-yield efficient synthetic methods and an evaluation of anticancer activity of halogenated noscapine analogs. Our results show that all analogs display higher tubulin-binding activity than noscapine and inhibit proliferation of human cancer cells (MCF-7, MDA-MB-231 and CEM). Surprisingly, the bromo-analog is not, vert, similar40-fold more potent than noscapine in inhibiting cellular proliferation of MCF-7 cells. The ability of these analogs to inhibit cellular proliferation is mediated by cell cycle arrest at the G2/M phase, in that all analogs except 9-iodonoscapine, caused selective mitotic arrest with a higher efficiency than noscapine followed by apoptotic cell death as shown by immunofluorescence and quantitative FACS analyses. Furthermore, our results reveal the appearance of numerous fragmented nuclei as evidenced by DAPI staining. Thus, our data indicate a great potential of these compounds for studying microtubule-mediated processes and as chemotherapeutic agents for the management of human cancers.
 
Publisher Elsevier
 
Date 2009-04-24T09:12:19Z
2011-12-08T06:26:55Z
2011-12-26T13:01:37Z
2011-12-27T05:45:35Z
2009-04-24T09:12:19Z
2011-12-08T06:26:55Z
2011-12-26T13:01:37Z
2011-12-27T05:45:35Z
2006
 
Type Article
 
Identifier Biochemical Pharmacology 72(4), 415-426
0006-2952
10.1016/j.bcp.2006.05.004
http://hdl.handle.net/10054/1232
http://dspace.library.iitb.ac.in/xmlui/handle/10054/1232
 
Language en