Adriamycin prodrugs

This field was recently reviewed [172]. Enzymes that have been used for ADEPT are, e.g., alkaline phosphatase, carboxypeptidase A, cytosine deaminase, -lactamase prodrugs and corresponding drugs were, e.g., adriamycin phosphate and adriamycin, methotrexate-alanine and methotrexate, 5-fluorocytosine and 5-fluorouracil, and vinca-cephalosporin and vinca alkaloid [172 and references therein]. 

There have been also attempts to prepare targeted drugs based on anthracyclines employing the recognition of some specific sugars by receptors on the tumor cells. Thus, a /3-glucoside derivative of adriamycin (41) was used in an antibody-directed enzyme-prodrug therapy (O Scheme 16) [53],... 

There is complete reduction of a p- or o-quinone to the corresponding hydroquinone or catechol, respectively. In the human liver, carbonyl reductase may play a role in the reduction of some quinones. Catechols are primary substrates for catechol o-me-thyl transferase, but also undergo sulfation. However, for the antitumor quinones, mitomycin C, adriamycin, and daunomycin, two-electron reduction serves as an efficient bioactivation mechanism, elegantly affirming the concept of bioreductive alkylation for the preferential bioactivation of antitumor prodrugs with oxygen deficient tumors. 

Hoes CJT, Potman W, van Heeswijk WAR, Mud J, de Grooth B-G, Grave I, Feijen J. Optimization of macromolecular prodrugs of the antitumor antibiotic adriamycin. J Contr Rel 1985 2 205-213. 

Nukui, M., Hoes, K., Vandenberg, H. and Feijen, J. (1991) Association of macromolecular prodrugs consisting of adriamycin bound to poly(L-glutamic acid), Macromol. Chem. 192, 2925-2942. 

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