Document Detail


Synthesis and anticancer activity of a series of norcantharidin analogues.
MedLine Citation:
PMID:  22796041     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Cantharidin (1) and norcantharidin (2) display high levels of anticancer activity against a broad range of tumour cell lines. Synthetic manipulation of norcantharidin yields (3S,3aR,4S,7R,7aS)-3-hydroxyhexahydro-4,7-epoxyisobenzofuran-1(3H)-one (3), which also displays a high level of anticancer activity against tumour cells but interestingly, shows selectivity towards HT29 (colon; GI(50) = 14 μM) and SJ-G2 (glioblastoma; GI(50) = 15 μM) cell lines. Substitution at the hydroxyl group of the cyclic lactone within (3) produces a diasteromeric pair of products that have no difference in cytotoxicity over the cell lines tested. Incorporation of an isopropyl tail at this position (16) produced the most promising compound of this series to date, with strong selectivity towards HT29 (colon; GI(50) = 19 μM) and SJ-G2 (glioblastoma; GI(50) = 21 μM) cell lines but completely void of any activity against the remaining tumour cell lines (GI(50) > 100 μM), as per the parent molecule. We also discovered that the introduction of a terminal phosphate moiety (28) at the same position produced a different trend in cytotoxicity with strong activity in BE2-C (neuroblastoma; GI(50) = 9 μM) cells; suggestive of an alternate mode of action.
Authors:
Mark Tarleton; Jayne Gilbert; Jennette A Sakoff; Adam McCluskey
Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2012-6-15
Journal Detail:
Title:  European journal of medicinal chemistry     Volume:  -     ISSN:  1768-3254     ISO Abbreviation:  -     Publication Date:  2012 Jun 
Date Detail:
Created Date:  2012-7-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0420510     Medline TA:  Eur J Med Chem     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Crown Copyright © 2012. Published by Elsevier Masson SAS. All rights reserved.
Affiliation:
Chemistry, Centre for Chemical Biology, School of Environmental & Life Sciences, University of Newcastle, University Drive, Callaghan NSW 2308, Australia.
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