Dendritic prodrug system

We decided to apply the elimination-based dendritic system to the synthesis of an anticancer prodrug and to evaluate it in a tumor cell cytotoxicity assay. Dendritic prodrugs 20 and 21 were synthesized with the chemotherapeutic drug melphalan as a tail unit and a trigger that is activated by PGA (Fig. 5.14). 

To further explore the advantages of a dendritic prodrug platform we synthesized a new system, based on an AB3 dendritic imit (Scheme 21), where three drug molecules (B) are finked to one enzymatic substrate (A). The trigger is activated upon enzymatic cleavage and is designed to release the three... 

As an example of a selectively acting drug carrier, we would like to mention also the PDEPT (polymer-directed enzyme prodrug therapy) approach based on combination of HPMA copolymer prodrug with the poly(HPMA)-enzyme conjugate selectively generating the cytotoxic drug within tumor. As an example a combination of PKl and polymer-cathepsin B system can be cited but also other combinations were tested. HPMA-based polymers with a micellar or dendritic structure have been also intensively studied they are described in separate chapters. 

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