| 摘要 |
Metallic derivatives of anthracycline glycosides such as doxorubicin and daunorubicin are prepared by admixing divalent or trivalent metal cations, preferably Fe(III), with the glycoside and adjusting pH to promote chelation of the metal by bidentate ligands of the glycoside. The derivatives are isolated in essentially monomeric form, and preferably lyophilized for later reconstitution immediately before use in the treatment of transplanted tumors in mice. As compared with the parent glycosides, the derivatives exhibit greatly diminished cardiotoxicity and less general, hematological and digestive toxicity as well. At the same time, the antineoplastic efficacy of the derivatives in transplanted mouse tumor test systems appears to be approximately equivalent to that of the parent glycoside on a mg. to mg. basis. As a result, the therapeutic index of the derivative is greatly elevated over that of the parent, since the derivative may be safely administered in greater quantities. |
