Synthesis and Selective Anticancer Activity of Organochalcogen Based Redox Catalysts
Posted on 2010-10-14 - 00:00
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.
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Doering, Mandy; Ba, Lalla A.; Lilienthal, Nils; Nicco, Carole; Scherer, Christiane; Abbas, Muhammad; et al. (2016). Synthesis and Selective Anticancer Activity of Organochalcogen Based Redox Catalysts. ACS Publications. Collection. https://doi.org/10.1021/jm100576z
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AUTHORS (14)
MD
Mandy Doering
LB
Lalla A. Ba
NL
Nils Lilienthal
CN
Carole Nicco
CS
Christiane Scherer
MA
Muhammad Abbas
AA
Abdul Ali Peer Zada
RC
Romain Coriat
TB
Torsten Burkholz
LW
Ludger Wessjohann
MD
Marc Diederich
FB
Frederic Batteux
MH
Marco Herling
CJ
Claus Jacob
KEYWORDS
substrate specificity promiseRedox CatalystsMany tumor cells exhibitleukemic cellstumor cell culturestumor entitiesanimal modelsmicromolar concentrationsanticancer activityCLL cellscell linescancer cellsROS levelsreactive oxygen speciescatalysts actnonmalignant counterpartsredox agentsPBMCROS amplificationdecrease cell proliferationnovel organochalcogencarcinoma cell linesintracellular redox stateSelective Anticancer Activitytumor initiationchemotherapeutic drugs