Document Detail


Synthesis and selective anticancer activity of organochalcogen based redox catalysts.
MedLine Citation:
PMID:  20836556     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Many tumor cells exhibit a disturbed intracellular redox state resulting in higher levels of reactive oxygen species (ROS). As these contribute to tumor initiation and sustenance, catalytic redox agents combining significant activity with substrate specificity promise high activity and selectivity against oxidatively stressed malignant cells. We describe here the design and synthesis of novel organochalcogen based redox sensor/effector catalysts. Their selective anticancer activity at submicromolar and low micromolar concentrations was established here in a range of tumor entities in various biological systems including cell lines, primary tumor cell cultures, and animal models. In the B-cell derived chronic lymphocytic leukemia (CLL), for instance, such compounds preferentially induce apoptosis in the cancer cells while peripheral blood mononuclear cells (PBMC) from healthy donors and the subset of normal B-cells remain largely unaffected. In support of the concept of sensor/effector based ROS amplification, we are able to demonstrate that underlying this selective activity against CLL cells are pre-existing elevated ROS levels in the leukemic cells compared to their nonmalignant counterparts. Furthermore, the catalysts act in concert with certain chemotherapeutic drugs in several carcinoma cell lines to decrease cell proliferation while showing no such interactions in normal cells. Overall, the high efficacy and selectivity of (redox) catalytic sensor/effector compounds warrant further, extensive testing toward transfer into the clinical arena.
Authors:
Mandy Doering; Lalla A Ba; Nils Lilienthal; Carole Nicco; Christiane Scherer; Muhammad Abbas; Abdul Ali Peer Zada; Romain Coriat; Torsten Burkholz; Ludger Wessjohann; Marc Diederich; Frederic Batteux; Marco Herling; Claus Jacob
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Journal of medicinal chemistry     Volume:  53     ISSN:  1520-4804     ISO Abbreviation:  J. Med. Chem.     Publication Date:  2010 Oct 
Date Detail:
Created Date:  2010-10-07     Completed Date:  2010-11-09     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9716531     Medline TA:  J Med Chem     Country:  United States    
Other Details:
Languages:  eng     Pagination:  6954-63     Citation Subset:  IM    
Affiliation:
Division of Bioorganic Chemistry, School of Pharmacy, Saarland University, D-66123 Saarbruecken, Germany.
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MeSH Terms
Descriptor/Qualifier:
Animals
Antineoplastic Agents / chemical synthesis*,  chemistry,  pharmacology
Apoptosis / drug effects
Catalysis
Cell Line
Cell Line, Tumor
Drug Screening Assays, Antitumor
Humans
Leukemia, Lymphocytic, Chronic, B-Cell / metabolism,  pathology
Leukocytes, Mononuclear / drug effects
Mice
Naphthoquinones / chemical synthesis,  chemistry,  pharmacology
Organoselenium Compounds / chemical synthesis*,  chemistry,  pharmacology
Oxidation-Reduction
Quinones / chemical synthesis*,  chemistry,  pharmacology
Reactive Oxygen Species / metabolism
Structure-Activity Relationship
Sulfides / chemical synthesis*,  chemistry,  pharmacology
Tellurium*
Chemical
Reg. No./Substance:
0/Antineoplastic Agents; 0/Naphthoquinones; 0/Organoselenium Compounds; 0/Quinones; 0/Reactive Oxygen Species; 0/Sulfides; 13494-80-9/Tellurium

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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