Synthesis and stability of four maleimide derivatives of the anticancer drug doxorubicin for the preparation of chemoimmunoconjugates

Article abstract of DOI:10.1248/cpb.45.399

By attaching maleimide groups to anticancer drugs, derivatives are obtained which bind selectively to thiolated carrier proteins. Four maleimide derivatives of the anticancer drug doxorubicin were prepared in which 3- maleimidobenzoic acid or 4-maleimidophenylacetic acid was bound to the 3'- amino position of doxorubicin through a benzoyl or phenylacetyl amide bond (1 or 2) or in which 3-maleimidobenzoic acid hydrazide or 4- maleimidophenylacetic acid hydrazide was bound to the 13-keto position through a benzoyl or phenylacetyl hydrazone bond (3 or 4). The maleimide derivatives of doxorubicin were characterized by means of ¹³C-NMR spectroscopy, elemental analysis and mass spectrometry. In addition, the stability of the maleimide derivatives 1-4 at pH values of 5.0 and 7.4 was investigated with the aid of HPLC. The amide or hydrazone bond of 1-4 is stable at pH 7.4 whereas the hydrazone bond is acid-sensitive.

Full text of DOI:10.1248/cpb.45.399

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