Academia Sinica

Zeljko M Prijovic

Steve R Roffler

Yu-Lin Leu

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 &#x3b2;-glucuronidases. BQC-G was about 30 times less toxic than BQC, but was as toxic as BQC after hydrolysis of the glucuronide moiety by &#x3b2;-glucuronidase. In the presence of human serum albumin, BQC-G displayed lower cytotoxicity (IC=1080 nM) but could be activated by &#x3b2;-glucuronidase to display potent activity (IC=13.3 nM).

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Taipei, Taiwan

Zeljko M Prijovic