N-Succinyl-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin: an extracellularly tumor-activated prodrug devoid of intravenous acute toxicity.
(2001) Journal of Medicinal Chemistry — Vol. 44, n° 22, p. 3750-3753 (2001)
Files
pdfdocument.pdf
Restricted Access - Adobe PDF
- 99.88 KB
Details
- Authors
- Abstract
- Intravenous administration of N-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin (4) induces an acute toxic reaction, killing animals in a few minutes. This results from its positive charge at physiological pH combined with its propensity to form large aggregates in aqueous solutions. Negatively charged N-capped versions of 4 such as the succinyl derivative 5 can be administered by the iv route at more than 10 times the LD(50) of doxorubicin without inducing the acute toxic reaction, and they are active in vivo.
- Affiliations
Citations
Fernandez, A. M., Van Derpoorten, K., Dasnois, L., Lebtahi, K., Dubois, V., Lobl, T. J., Gangwar, S., Oliyai, C., Lewis, E. R., Shochat, D., & Trouet, A. (2001). N-Succinyl-(beta-alanyl-L-leucyl-L-alanyl-L-leucyl)doxorubicin: an extracellularly tumor-activated prodrug devoid of intravenous acute toxicity. Journal of Medicinal Chemistry, 44(22), 3750-3753. https://doi.org/10.1021/jm0108754 (Original work published 2001)