TY - JOUR
T1 - Novel anthraquinone derivatives with redox-active functional groups capable of producing free radicals by metabolism
T2 - Are free radicals essential for cytotoxicity?
AU - Barasch, Dinorah
AU - Zipori, Omer
AU - Ringel, Israel
AU - Ginsburg, Isaac
AU - Samuni, Amram
AU - Katzhendler, Jehoshua
PY - 1999/7
Y1 - 1999/7
N2 - The mode of action of antitumour anthraquinone derivatives (i.e. mitoxantrone) is not clearly established yet. It includes, among others, intercalation and binding to DNA, bioreduction and aerobic redox cycling. A series of anthraquinone derivatives, with potentially bioreducible groups sited in the side chain, have been synthesized and biologically evaluated. Their redox and cytotoxic activities were screened. Derivatives which bear a 2-(dimethylamino)ethylamino substituent, known to confer high DNA affinity, demonstrated cytotoxicity but not redox activity (beside the anthraquinone reduction). Conversely, derivatives which showed redox activity were not cytotoxic toward the P388 cell line. The results suggest that bioreduction is not the main mode of action in the cytotoxicity of anthraquinones.
AB - The mode of action of antitumour anthraquinone derivatives (i.e. mitoxantrone) is not clearly established yet. It includes, among others, intercalation and binding to DNA, bioreduction and aerobic redox cycling. A series of anthraquinone derivatives, with potentially bioreducible groups sited in the side chain, have been synthesized and biologically evaluated. Their redox and cytotoxic activities were screened. Derivatives which bear a 2-(dimethylamino)ethylamino substituent, known to confer high DNA affinity, demonstrated cytotoxicity but not redox activity (beside the anthraquinone reduction). Conversely, derivatives which showed redox activity were not cytotoxic toward the P388 cell line. The results suggest that bioreduction is not the main mode of action in the cytotoxicity of anthraquinones.
KW - Anthraquinones
KW - Bioreduction
KW - Cytotoxicity
UR - http://www.scopus.com/inward/record.url?scp=0032710427&partnerID=8YFLogxK
U2 - 10.1016/S0223-5234(00)80029-X
DO - 10.1016/S0223-5234(00)80029-X
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C2 - 11278045
AN - SCOPUS:0032710427
SN - 0223-5234
VL - 34
SP - 597
EP - 615
JO - European Journal of Medicinal Chemistry
JF - European Journal of Medicinal Chemistry
IS - 7-8
ER -