Document Detail


Second generation benzofuranone ring substituted noscapine analogs: synthesis and biological evaluation.
MedLine Citation:
PMID:  21501599     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Microtubules, composed of α/β tubulin heterodimers, represent a validated target for cancer chemotherapy. Thus, tubulin- and microtubule-binding antimitotic drugs such as taxanes and vincas are widely employed for the chemotherapeutic management of various malignancies. Although quite successful in the clinic, these drugs are associated with severe toxicity and drug resistance problems. Noscapinoids represent an emerging class of microtubule-modulating anticancer agents based upon the parent molecule noscapine, a naturally occurring non-toxic cough-suppressant opium alkaloid. Here we report in silico molecular modeling, chemical synthesis and biological evaluation of novel analogs derived by modification at position-7 of the benzofuranone ring system of noscapine. The synthesized analogs were evaluated for their tubulin polymerization activity and their biological activity was examined by their antiproliferative potential using representative cancer cell lines from varying tissue-origin [A549 (lung), CEM (lymphoma), MIA PaCa-2 (pancreatic), MCF-7 (breast) and PC-3 (prostate)]. Cell-cycle studies were performed to explore their ability to halt the cell-cycle and induce subsequent apoptosis. The varying biological activity of these analogs that differ in the nature and bulk of substituent at position-7 was rationalized utilizing predictive in silico molecular modeling.
Authors:
Ram Chandra Mishra; Prasanthi Karna; Sushma Reddy Gundala; Vaishali Pannu; Richard A Stanton; Kamlesh Kumar Gupta; M Hope Robinson; Manu Lopus; Leslie Wilson; Maged Henary; Ritu Aneja
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, U.S. Gov't, Non-P.H.S.     Date:  2011-04-08
Journal Detail:
Title:  Biochemical pharmacology     Volume:  82     ISSN:  1873-2968     ISO Abbreviation:  Biochem. Pharmacol.     Publication Date:  2011 Jul 
Date Detail:
Created Date:  2011-06-06     Completed Date:  2011-08-05     Revised Date:  2013-06-30    
Medline Journal Info:
Nlm Unique ID:  0101032     Medline TA:  Biochem Pharmacol     Country:  England    
Other Details:
Languages:  eng     Pagination:  110-21     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 Elsevier Inc. All rights reserved.
Affiliation:
Department of Biology, Georgia State University, Atlanta, GA 30303, United States.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemical synthesis*,  pharmacology
Apoptosis / drug effects
Benzofurans / chemical synthesis*,  pharmacology
Cell Cycle / drug effects
Cell Line, Tumor
Cell Proliferation / drug effects
Computer Simulation
Humans
Models, Molecular
Noscapine / analogs & derivatives*,  chemical synthesis,  pharmacology
Protein Structure, Quaternary
Structure-Activity Relationship
Tubulin / chemistry
Tubulin Modulators / chemical synthesis*,  pharmacology
Grant Support
ID/Acronym/Agency:
K99 CA131489-01A1/CA/NCI NIH HHS; K99 CA131489-02/CA/NCI NIH HHS; K99 CA131489-02S1/CA/NCI NIH HHS; R00 CA131489/CA/NCI NIH HHS; R00 CA131489-03/CA/NCI NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Benzofurans; 0/Tubulin; 0/Tubulin Modulators; 128-62-1/Noscapine
Comments/Corrections

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