Universität zu Köln

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:	Creators Email ORCID ORCID Put Code Doering, Mandy UNSPECIFIED UNSPECIFIED UNSPECIFIED Ba, Lalla A. UNSPECIFIED UNSPECIFIED UNSPECIFIED Lilienthal, Nils UNSPECIFIED UNSPECIFIED UNSPECIFIED Nicco, Carole UNSPECIFIED orcid.org/0000-0001-8211-2556 UNSPECIFIED Scherer, Christiane UNSPECIFIED UNSPECIFIED UNSPECIFIED Abbas, Muhammad UNSPECIFIED UNSPECIFIED UNSPECIFIED Zada, Abdul Ali Peer UNSPECIFIED UNSPECIFIED UNSPECIFIED Coriat, Romain UNSPECIFIED UNSPECIFIED UNSPECIFIED Burkholz, Torsten UNSPECIFIED orcid.org/0000-0002-5497-368X UNSPECIFIED Wessjohann, Ludger UNSPECIFIED UNSPECIFIED UNSPECIFIED Diederich, Marc UNSPECIFIED orcid.org/0000-0003-0115-4725 UNSPECIFIED Batteux, Frederic UNSPECIFIED orcid.org/0000-0002-1265-7996 UNSPECIFIED Herling, Marco UNSPECIFIED UNSPECIFIED UNSPECIFIED Jacob, Claus UNSPECIFIED UNSPECIFIED UNSPECIFIED
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:	Keywords Language SUPEROXIDE-DISMUTASE; OXIDATIVE STRESS; 1ST-LINE TREATMENT; CELL-DEATH; CANCER; FLUOROURACIL; INHIBITORS; COMPOUND; DRUGS Multiple languages Chemistry, Medicinal Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49428