BQC-G, a tumor-selective anti-cancer prodrug

摘要

The invention relates to the synthesis of a second-generation camptothecin glucuronide prodrug (BQC-G) of a potent anticancer camptothecin derivative 5,6-dihydro-4H-benzo[de]quinoline-camptothecin (BQC). BQC-G was over 4000 times more water soluble than BQC, displayed good stability in human plasma and was an excellent substrate for enzymatic hydrolysis by bacterial and human β-glucuronidases. BQC-G was about 30 times less toxic than BQC, but was as toxic as BQC after hydrolysis of the glucuronide moiety by β-glucuronidase. In the presence of human serum albumin, BQC-G displayed lower cytotoxicity (IC50=1080 nM) but could be activated by β-glucuronidase to display potent activity (IC50=13.3 nM).

主权项

1. A compound according to the formula I, below: wherein R is a glucuronide linked via an immolative spacer, or a pharmaceutically acceptable salt thereof.