TY - JOUR
T1 - Hydrogen peroxide inducible DNA cross-linking agents
T2 - Targeted anticancer prodrugs
AU - Kuang, Yunyan
AU - Balakrishnan, Kumudha
AU - Gandhi, Varsha
AU - Peng, Xiaohua
PY - 2011/12/7
Y1 - 2011/12/7
N2 - The major concern for anticancer chemotherapeutic agents is the host toxicity. The development of anticancer prodrugs targeting the unique biochemical alterations in cancer cells is an attractive approach to achieve therapeutic activity and selectivity. We designed and synthesized a new type of nitrogen mustard prodrug that can be activated by high level of reactive oxygen species (ROS) found in cancer cells to release the active chemotherapy agent. The activation mechanism was determined by NMR analysis. The activity and selectivity of these prodrugs toward ROS was determined by measuring DNA interstrand cross-links and/or DNA alkylations. These compounds showed 60-90% inhibition toward various cancer cells, while normal lymphocytes were not affected. To the best of our knowledge, this is the first example of H 2O 2-activated anticancer prodrugs.
AB - The major concern for anticancer chemotherapeutic agents is the host toxicity. The development of anticancer prodrugs targeting the unique biochemical alterations in cancer cells is an attractive approach to achieve therapeutic activity and selectivity. We designed and synthesized a new type of nitrogen mustard prodrug that can be activated by high level of reactive oxygen species (ROS) found in cancer cells to release the active chemotherapy agent. The activation mechanism was determined by NMR analysis. The activity and selectivity of these prodrugs toward ROS was determined by measuring DNA interstrand cross-links and/or DNA alkylations. These compounds showed 60-90% inhibition toward various cancer cells, while normal lymphocytes were not affected. To the best of our knowledge, this is the first example of H 2O 2-activated anticancer prodrugs.
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U2 - 10.1021/ja2073824
DO - 10.1021/ja2073824
M3 - Article
C2 - 22035519
AN - SCOPUS:82555170608
SN - 0002-7863
VL - 133
SP - 19278
EP - 19281
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 48
ER -