Document Detail


Design and synthesis of Pictet-Spengler condensation products that exhibit oncogenic-RAS synthetic lethality and induce non-apoptotic cell death.
MedLine Citation:
PMID:  22832321     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
A series of Pictet-Spengler condensation derivatives (tetrahydro-β-carbolines) was designed, synthesized and evaluated for lethality against a panel of seven cancer cell lines. Seven compounds (2a, 13, 20, 21, 27, 29 and 34) showed lethality in at least five cell lines. Among these, compound 27 showed a unique selectivity towards oncogenic-RAS expressing BJ-TERT/LT/ST/RAS(V12) tumor cells, compared to non-transformed BJ-TERT cells. Further investigation revealed that 27 induces cell death without activation of caspases. This represents a useful new probe of non-apoptotic cell death and oncogenic-RAS synthetic lethality.
Authors:
Rachid Skouta; Miki Hayano; Kenichi Shimada; Brent R Stockwell
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2012-06-30
Journal Detail:
Title:  Bioorganic & medicinal chemistry letters     Volume:  22     ISSN:  1464-3405     ISO Abbreviation:  Bioorg. Med. Chem. Lett.     Publication Date:  2012 Sep 
Date Detail:
Created Date:  2012-08-20     Completed Date:  2013-01-07     Revised Date:  2013-09-03    
Medline Journal Info:
Nlm Unique ID:  9107377     Medline TA:  Bioorg Med Chem Lett     Country:  England    
Other Details:
Languages:  eng     Pagination:  5707-13     Citation Subset:  IM    
Copyright Information:
Copyright © 2012 Elsevier Ltd. All rights reserved.
Affiliation:
Department of Biological Sciences, Columbia University, 550 West 120th Street, Northwest Corner Building, MC 4846, New York, NY 10027, USA.
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MeSH Terms
Descriptor/Qualifier:
Antineoplastic Agents / chemical synthesis,  chemistry*,  pharmacology*
Carbolines / chemical synthesis,  chemistry*,  pharmacology*
Cell Death / drug effects
Cell Line, Tumor
Cell Survival / drug effects
Drug Design
Gene Expression Regulation, Neoplastic / drug effects
Genes, ras / drug effects*
Humans
Neoplasms / drug therapy*,  genetics
Grant Support
ID/Acronym/Agency:
R01 CA097061/CA/NCI NIH HHS; R01 CA161061/CA/NCI NIH HHS; R01 GM085081/GM/NIGMS NIH HHS; R01CA097061/CA/NCI NIH HHS; R01CA161061/CA/NCI NIH HHS; R01GM085081/GM/NIGMS NIH HHS
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Carbolines
Comments/Corrections

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