Doering, Mandy, Ba, Lalla A., Lilienthal, Nils, Nicco, Carole ORCID: 0000-0001-8211-2556, Scherer, Christiane, Abbas, Muhammad, Zada, Abdul Ali Peer, Coriat, Romain, Burkholz, Torsten ORCID: 0000-0002-5497-368X, Wessjohann, Ludger, Diederich, Marc ORCID: 0000-0003-0115-4725, Batteux, Frederic ORCID: 0000-0002-1265-7996, Herling, Marco and Jacob, Claus (2010). Synthesis and Selective Anticancer Activity of Organochalcogen Based Redox Catalysts. J. Med. Chem., 53 (19). S. 6954 - 6964. WASHINGTON: AMER CHEMICAL SOC. ISSN 1520-4804

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Abstract

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 atctivity with substrate specificity promise high activity andselectivity L. Must 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 13-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 CI.I. 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.

Item Type: Journal Article
Creators:
CreatorsEmailORCIDORCID Put Code
Doering, MandyUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Ba, Lalla A.UNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Lilienthal, NilsUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Nicco, CaroleUNSPECIFIEDorcid.org/0000-0001-8211-2556UNSPECIFIED
Scherer, ChristianeUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Abbas, MuhammadUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Zada, Abdul Ali PeerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Coriat, RomainUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Burkholz, TorstenUNSPECIFIEDorcid.org/0000-0002-5497-368XUNSPECIFIED
Wessjohann, LudgerUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Diederich, MarcUNSPECIFIEDorcid.org/0000-0003-0115-4725UNSPECIFIED
Batteux, FredericUNSPECIFIEDorcid.org/0000-0002-1265-7996UNSPECIFIED
Herling, MarcoUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
Jacob, ClausUNSPECIFIEDUNSPECIFIEDUNSPECIFIED
URN: urn:nbn:de:hbz:38-494281
DOI: 10.1021/jm100576z
Journal or Publication Title: J. Med. Chem.
Volume: 53
Number: 19
Page Range: S. 6954 - 6964
Date: 2010
Publisher: AMER CHEMICAL SOC
Place of Publication: WASHINGTON
ISSN: 1520-4804
Language: English
Faculty: Unspecified
Divisions: Unspecified
Subjects: no entry
Uncontrolled Keywords:
KeywordsLanguage
SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; 1ST-LINE TREATMENT; CELL-DEATH; CANCER; FLUOROURACIL; INHIBITORS; COMPOUND; DRUGSMultiple languages
Chemistry, MedicinalMultiple languages
URI: http://kups.ub.uni-koeln.de/id/eprint/49428

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