| Second generation benzofuranone ring substituted noscapine analogs: synthesis and biological evaluation. | |
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MedLine Citation:
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PMID: 21501599 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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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:
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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:
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Title: Biochemical pharmacology Volume: 82 ISSN: 1873-2968 ISO Abbreviation: Biochem. Pharmacol. Publication Date: 2011 Jul |
Date Detail:
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Created Date: 2011-06-06 Completed Date: 2011-08-05 Revised Date: 2012-09-24 |
Medline Journal Info:
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Nlm Unique ID: 0101032 Medline TA: Biochem Pharmacol Country: England |
Other Details:
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Languages: eng Pagination: 110-21 Citation Subset: IM |
Copyright Information:
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Copyright © 2011 Elsevier Inc. All rights reserved. |
Affiliation:
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Department of Biology, Georgia State University, Atlanta, GA 30303, United States. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Antineoplastic Agents
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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:
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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:
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0/Antineoplastic Agents; 0/Benzofurans; 0/Tubulin; 0/Tubulin Modulators; 128-62-1/Noscapine |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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