I
present knowledge and state-of-the-art in
chemotherapy and thermotherapy lead us to
recommend clinical trials of this therapy com­
bination in selected osteogenic sarcoma
patients.
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1971.
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B. D. A llan
R- L. Norman
United States Arm y Missile
Command
Redstone Arsenal, Ala 33809
September 9. 1071
D ig it iz e d b y Google
Another Hypothesis Concerning the Antitumor
Activity and Cerdlotoxiclty of Daunorubicin
(NSC-82151) and Adriam ycin (NSC-123127)'
Adamson (1) recently suggested that the
cardiotoxicity of adriamycin (la ) and dauno-
rubicin (lb ) can be attributed to the daunosa-
mine (2) portion of the molecules, and that
compounds in which the aglycones bear an
amine or alkylamine group might show anti­
tumor activity with no cardiotoxicity. The re­
sults of Müller et al (2) with alkylaminoan-
thraquinones support Adamson's ideas.
0 oh ^
La R>0H; R* « d j< in o » a » ln « > (2 )
lb R "H ; R* » d i u n o i M l u (2 )
I should like to present another (but not con­
flicting) suggestion. The anticancer activity of
adriamycin and daunorubicin is probably con­
nected with their ability to form intercalated
complexes with DNA (3-10). The formation of |
the complexes appears to involve the amino
sugar group and the quinone chromophore of
la and lb. Mhatre et al (11,12) and Yesair et
al (13) have provided evidence that the cardio-
toxic properties associated with la and lb are
related to the formation of aglycones in the
heart, and that the cleavage to the aglycones is
more rapid for la and lb than for N-acetyl-
daunomycin, which does not interact well with
DNA and does not show as much anticancer
activity as lb. I suggest the following explana­
tion for the effect of the interaction of la or
lb with DNA on the stability of the glycoside
link. The structure of lb determined by X-ray
crystallography (14) shows that the hydroxyl
group at C, is strongly hydrogen-bonded to the
quinone carbonyl group at C,. Since intercala­
tion involves the quinone system, it is possible
that the hydrogen bond between O . and O* is no
'D aunorubicin: CA S re*r. No. 23541-50-6; daunomy-
cin; rubidomycin (NSC-83142).
fifttfp o th era p y Reports Part 1