Document Detail

New substituted 4H-chromenes as anticancer agents.
MedLine Citation:
PMID:  22608389     Owner:  NLM     Status:  MEDLINE    
As a continuation of our efforts to discover and develop small molecules as anticancer agents, we identified GRI-394837 as an initial hit from similarity search on RGD and its analogs. Based on GRI-394837, we designed and synthesized a focused set of novel chromenes (4a-e) in a single step using microwave method. All five compounds showed activity in the nanomolar range (IC(50): 7.4-640 nM) in two melanoma, three prostate and four glioma cancer cell lines. The chromene 4e is active against all the cell lines and particularly against the A172 human glioma cell line (IC(50): 7.4 nM). Interestingly, in vitro tubulin polymerization assay shows 4e to be a weak tubulin polymerization inhibitor but it shows very strong cytotoxicity in cellular assays, therefore there must be additional unknown mechanism(s) for the anticancer activity. Additionally, the strong antiproliferative activity was verified by one of the selected chromene (4a) by the NCI 60 cell line screen. These results strongly suggest that the novel chromenes could be further developed as a potential therapeutic agent for a variety of aggressive cancers.
Shivaputra A Patil; Jin Wang; Xiaochen S Li; Jianjun Chen; Terreia S Jones; Amira Hosni-Ahmed; Renukadevi Patil; William L Seibel; Wei Li; Duane D Miller
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-04-24
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  22     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-15     Completed Date:  2012-10-19     Revised Date:  2013-07-03    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  4458-61     Citation Subset:  IM    
Copyright Information:
Copyright © 2012. Published by Elsevier Ltd.
Department of Pharmaceutical Sciences, College of Pharmacy, The University of Tennessee Health Science Center, Memphis, TN 38163, USA.
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MeSH Terms
Antineoplastic Agents / chemical synthesis,  chemistry*,  toxicity
Astrocytes / drug effects
Benzopyrans / chemical synthesis,  chemistry*,  toxicity
Binding Sites
Cell Line, Tumor
Cell Proliferation / drug effects
Computer Simulation
Drug Screening Assays, Antitumor
Oligopeptides / chemistry
Protein Structure, Tertiary
Tubulin / chemistry,  metabolism
Tubulin Modulators / chemical synthesis,  chemistry,  toxicity
Grant Support
1R01CA148706/CA/NCI NIH HHS; R01 CA148706/CA/NCI NIH HHS; S10 RR026377/RR/NCRR NIH HHS
Reg. No./Substance:
0/2-amino-4-(5-bromo-2-methoxyphenyl)-7-hydroxy-4H-chromene-3-carbonitrile; 0/Antineoplastic Agents; 0/Benzopyrans; 0/Oligopeptides; 0/Tubulin; 0/Tubulin Modulators; 99896-85-2/arginyl-glycyl-aspartic acid

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