TY - JOUR
T1 - In vitro and in vivo Immunosuppressive Activity of a Novel Anthracycline, 13-deoxy, 5-iminodoxorubicin
AU - Olson, Richard D.
AU - Headley, Mark B.
AU - Hodzic, Alma
AU - Walsh, Gerald M.
AU - Wingett, Denise G.
PY - 2007/6/1
Y1 - 2007/6/1
N2 - We report that the novel anthracycline analog, 13-deoxy, 5-iminodoxorubicin (DIDOX), represents a potentially new class of immunosuppressive agents. DIDOX has been structurally modified from the parent compound, doxorubicin, to remove the carbonyl group at carbon-13 and the quinone moiety at carbon-5 since these structures likely mediate the cardiotoxic side effects of this family of chemotherapeutic drugs. Our studies demonstrate that DIDOX inhibits T cell proliferation and the expression of the T cell activation molecules, CD25 and CD40L. DIDOX also inhibits the production of the pro-inflammatory cytokine, TNF-α and IL-2. Studies using animal models demonstrate that DIDOX inhibits the inflammation accompanying contact hypersensitivity reactions and possesses reduced cardiotoxicity compared to doxorubicin. These findings indicate that DIDOX has important immunosuppressive activities that may warrant the development of this new and improved anthracycline for the treatment of T cell-mediated inflammatory diseases.
AB - We report that the novel anthracycline analog, 13-deoxy, 5-iminodoxorubicin (DIDOX), represents a potentially new class of immunosuppressive agents. DIDOX has been structurally modified from the parent compound, doxorubicin, to remove the carbonyl group at carbon-13 and the quinone moiety at carbon-5 since these structures likely mediate the cardiotoxic side effects of this family of chemotherapeutic drugs. Our studies demonstrate that DIDOX inhibits T cell proliferation and the expression of the T cell activation molecules, CD25 and CD40L. DIDOX also inhibits the production of the pro-inflammatory cytokine, TNF-α and IL-2. Studies using animal models demonstrate that DIDOX inhibits the inflammation accompanying contact hypersensitivity reactions and possesses reduced cardiotoxicity compared to doxorubicin. These findings indicate that DIDOX has important immunosuppressive activities that may warrant the development of this new and improved anthracycline for the treatment of T cell-mediated inflammatory diseases.
KW - T lymphocytes
KW - anthracycline
KW - immunosuppression
UR - https://scholarworks.boisestate.edu/bio_facpubs/71
UR - http://dx.doi.org/10.1016/j.intimp.2007.01.010
U2 - 10.1016/j.intimp.2007.01.010
DO - 10.1016/j.intimp.2007.01.010
M3 - Article
C2 - 17466907
JO - International Immunopharmacology
JF - International Immunopharmacology
ER -