A new prodrug of paclitaxel: synthesis of Protaxel.

Abstract

2' and 7 Polyol carbonates of paclitaxel were synthesized and screened as potential paclitaxel prodrugs. Paclitaxel is released from 7-(2",3"-dihydroxypropylcarbonato) paclitaxel (Protaxel) at rates inversely proportional to pH, by an intramolecular cyclization. Compared to paclitaxel, maximum tolerated i.v. or i.p. doses (MTD) of Protaxel are about 2.5- to 3-fold higher; its efficacy is substantially higher in human cancer line xenografts in athymic mice, especially in prostate PC-3, breast MDA-MB 468 and ovary OVCAR-1.

• Authors: A L Seligson, R C Terry, J C Bressi, J G Douglass 3rd, M Sovak
• Journal: Anti-cancer drugs (Anticancer Drugs) Vol. 12 Issue 4 Pg. 305-13 (Apr 2001) ISSN: 0959-4973 [Print] England
• PMID: 11335786 (Publication Type: Comparative Study, Journal Article)

Chemical References

• Antineoplastic Agents
• Prodrugs
• Taxoids
• protaxel
• Paclitaxel

Topics

• Animals
• Antineoplastic Agents (chemical synthesis, pharmacology, toxicity)
• Breast Neoplasms (drug therapy)
• Cell Division (drug effects)
• Drug Stability
• Drug Tolerance
• Female
• Half-Life
• Humans
• Hydrogen-Ion Concentration
• Male
• Maximum Tolerated Dose
• Mice
• Mice, Inbred BALB C
• Mice, Nude
• Ovarian Neoplasms (drug therapy)
• Paclitaxel (analogs & derivatives, chemical synthesis, pharmacology, toxicity)
• Prodrugs (chemical synthesis, pharmacology, toxicity)
• Prostatic Neoplasms (drug therapy)
• Rats
• Rats, Sprague-Dawley
• Solubility
• Taxoids
• Xenograft Model Antitumor Assays