10.1021/jm100576z.s001
Mandy Doering
Mandy
Doering
Lalla A. Ba
Lalla A.
Ba
Nils Lilienthal
Nils
Lilienthal
Carole Nicco
Carole
Nicco
Christiane Scherer
Christiane
Scherer
Muhammad Abbas
Muhammad
Abbas
Abdul Ali Peer Zada
Abdul
Ali Peer Zada
Romain Coriat
Romain
Coriat
Torsten Burkholz
Torsten
Burkholz
Ludger Wessjohann
Ludger
Wessjohann
Marc Diederich
Marc
Diederich
Frederic Batteux
Frederic
Batteux
Marco Herling
Marco
Herling
Claus Jacob
Claus
Jacob
Synthesis and Selective Anticancer Activity of Organochalcogen Based Redox Catalysts
American Chemical Society
2010
substrate specificity promise
Redox CatalystsMany tumor cells exhibit
leukemic cells
tumor cell cultures
tumor entities
animal models
micromolar concentrations
anticancer activity
CLL cells
cell lines
cancer cells
ROS levels
reactive oxygen species
catalysts act
nonmalignant counterparts
redox agents
PBMC
ROS amplification
decrease cell proliferation
novel organochalcogen
carcinoma cell lines
intracellular redox state
Selective Anticancer Activity
tumor initiation
chemotherapeutic drugs
2010-10-14 00:00:00
Journal contribution
https://acs.figshare.com/articles/journal_contribution/Synthesis_and_Selective_Anticancer_Activity_of_Organochalcogen_Based_Redox_Catalysts/2722018
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.