New Taxol ® (paclitaxel) prodrugs designed for ADEPT and PMT strategies in cancer chemotherapy

Two new glucuronide paclitaxel prodrugs were synthesized. One of them fulfils all the stability and enzymatic cleavage requirements for an ADEPT or a PMT strategy in cancer chemotherapy. Two new glucuronide paclitaxel prodrugs have been synthesized. Linked to the 2′-OH of the drug by a carbonate function, they include a self-immolative spacer bearing an arylnitro or arylamino group between the drug and the glucuronic acid residue. Both prodrugs were well detoxified and easily cleaved in the presence of β- d-glucuronidase with fast removal of the spacer, releasing paclitaxel. The arylamino spacer-containing prodrug, more stable than the corresponding nitro analogue, was selected for further studies.