Paclitaxel esters of malic acid as prodrugs with improved water solubility

Authors
Damen, EWP Wiegerinck, PHG Braamer, L Sperling, D de Vos, D Scheeren, HW
Citation
Ewp. Damen et al., Paclitaxel esters of malic acid as prodrugs with improved water solubility, BIO MED CH, 8(2), 2000, pp. 427-432
Citations number
24
Categorie Soggetti
Chemistry & Analysis
Journal title
BIOORGANIC & MEDICINAL CHEMISTRY
ISSN journal
09680896 → ACNP
Volume
8
Issue
2
Year of publication
2000
Pages
427 - 432
Database
ISI
SICI code
0968-0896(200002)8:2<427:PEOMAA>2.0.ZU;2-8
Abstract
The synthesis of paclitaxel eaters of malic acid is described. These compou nds were found to have improved water solubility and are stable in solution at neutral pH. The C2' modified compounds behave as prodrugs, that is, pac litaxel is generated upon exposure to human plasma, whereas the C7 modified derivatives do not. 2'-Malyl paclitaxel sodium salt demonstrated enhanced antitumour activity and less toxicity in a P388 murine leukaemia in vivo mo del when compared to paclitaxel. (C) 2000 Elsevier Science Ltd. All rights reserved.