1. ¹Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115
2. ²ICTM, Center for Chemistry, Belgrade, Yugoslavia
3. ³School of Pharmacy, National Taiwan University, Taipei, Taiwan
4. ⁴Chia-Nan College of Pharmacy and Science, Tainan Hsien, Taiwan

Correspondence: S Roffler, E-mail: sroff@ibms.sinica.edu.tw

Received 8 May 2001; Revised 18 March 2002; Accepted 21 March 2002.

Abstract

Cancer chemotherapy is limited by the modest therapeutic index of most antineoplastic drugs. Some glucuronide prodrugs may display selective anti-tumour activity against tumours that accumulate -glucuronidase. We examined the toxicity and anti-tumour activity of 9-aminocamptothecin glucuronide, a new glucuronide prodrug of 9-aminocamptothecin, to evaluate its potential clinical utility. 9-aminocamptothecin glucuronide was 25–60 times less toxic than 9-aminocamptothecin to five human cancer cell lines. -glucuronidase activated 9-aminocamptothecin glucuronide to produce similar cell killing as 9-aminocamptothecin or topotecan. The in vivo toxicity of 9-aminocamptothecin glucuronide in BALB/c mice was dose-, route-, sex- and age-dependent. 9-aminocamptothecin glucuronide was significantly less toxic to female than to male mice but the difference decreased with age. 9-aminocamptothecin glucuronide and 9-aminocamptothecin produced similar inhibition (80%) of LS174T human colorectal carcinoma tumours. 9-aminocamptothecin glucuronide cured a high percentage of CL1-5 human lung cancer xenografts with efficacy that was similar to or greater than 9-aminocamptothecin, irinotecan and topotecan. The potent anti-tumour activity of 9-aminocamptothecin glucuronide suggests that this prodrug should be further evaluated for cancer treatment.