NEW DOXORUBICIN ANALOGS ACTIVE AGAINST DOXORUBICIN-RESISTANT COLON-TUMOR XENOGRAFTS IN THE NUDE-MOUSE

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  • 1 January 1980
    • journal article
    • research article
    • Vol. 40  (12) , 4682-4687
Abstract
The antitumor activity of doxorubicin and 3 new derivatives modified on the position 4'' of the amino sugar was tested against 5 human colon tumors and 2 human rectal tumors (originating from different patients) and xenografted into nude mice. The following drugs were tested: 4''-epidoxorubicin; 4''-deoxydoxorubicin; 4''-O-methyldoxorubicin. Mice were treated i.v. on a weekly basis for 3 to 4 wk, starting when the tumors were well established (advanced stage of tumor treatment). No statistically significant effect was observed against the tumor tested with the drug doxorubicin and 4''-epidoxorubicin. 4''-Deoxydoxorubicin was active against all the colon tumors tested (4 of 5 statistically significant); 4''-O-methyldoxorubicin was active against 4 of 5 colon tumors tested (statistically significant). The activity of 4''-O-methyldoxorubicin was less than that of 4''-deoxydoxorubicin against the colon carcinomas tested. Neither analog was active against the 2 rectal carcinomas tested. The modifications in the chemical structure of doxorubicin apparently can alter the biological properties and create new drugs varying in activity against different human tumors. The 2 antracycline derivatives, 4''-deoxydoxorubicin and 4''-O-methyldoxorubicin, appear to be good candidates for clinical trial against colon carcinoma. The nude mice system apparently offers a great potential for identification of new anthracycline analogs and, in general, new anticancer agents of clinical interest.