Paclitaxel esters of malic acid as prodrugs with improved water solubility

E W Damen; P H Wiegerinck; L Braamer; D Sperling; D de Vos; H W Scheeren

doi:10.1016/s0968-0896(99)00301-6

Paclitaxel esters of malic acid as prodrugs with improved water solubility

Bioorg Med Chem. 2000 Feb;8(2):427-32. doi: 10.1016/s0968-0896(99)00301-6.

Authors

E W Damen¹, P H Wiegerinck, L Braamer, D Sperling, D de Vos, H W Scheeren

Affiliation

¹ Department of Organic Chemistry, NSR Center for Molecular Structure, Design and Synthesis, University of Nijmegen, Toernooiveld, The Netherlands.

PMID: 10722165
DOI: 10.1016/s0968-0896(99)00301-6

Abstract

The synthesis of paclitaxel esters of malic acid is described. These compounds were found to have improved water solubility and are stable in solution at neutral pH. The C2' modified compounds behave as prodrugs, that is, paclitaxel 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 model when compared to paclitaxel.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antineoplastic Agents, Phytogenic / chemistry
Antineoplastic Agents, Phytogenic / pharmacology*
Esters
Humans
Magnetic Resonance Spectroscopy
Malates / chemistry*
Mice
Paclitaxel / chemistry
Paclitaxel / pharmacology*
Prodrugs / chemistry
Prodrugs / pharmacology*
Solubility
Spectrometry, Mass, Fast Atom Bombardment
Water

Substances

Antineoplastic Agents, Phytogenic
Esters
Malates
Prodrugs
Water
malic acid
Paclitaxel