Thiolo-, thiono- and dithiocarbonate and thiocarbamate derivatives of demethylpenclomedine as novel anticancer agents.

Abstract

PURPOSE:

The purpose of this investigation was to synthesize a series of thiolo-, thiono- and dithiocarbonate and thiocarbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma metabolite of penclomedine (PEN) in patients observed subsequently to be an active antitumor agent and non-neurotoxic in a rat model, in order to compare their antitumor activity with that of DM-PEN.

METHODS:

Derivatives were prepared from DM-PEN and evaluated in vivo against human MX-1 breast tumor xenografts implanted in the mammary fat pad, several of which were also evaluated against human brain tumor xenografts.

RESULTS:

Thiolocarbonate and thiocarbamate derivatives were found to be superior to DM-PEN against MX-1 tumor and modestly active against glioblastoma.

CONCLUSION:

The activity of the thiolocarbonates and thiocarbamates against human tumor xenografts in vivo suggests consideration of these two series of derivatives of DM-PEN for clinical development.

• Authors: Robert F Struck, William R Waud
• Journal: Cancer chemotherapy and pharmacology (Cancer Chemother Pharmacol) Vol. 57 Issue 2 Pg. 180-4 (Jan 2006) ISSN: 0344-5704 [Print] Germany
• PMID: 16096790 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)

Chemical References

• Antineoplastic Agents
• Carbamates
• Carbonates
• Picolines
• penclomedine

Topics

• Animals
• Antineoplastic Agents (pharmacology)
• Breast Neoplasms (drug therapy)
• Carbamates
• Carbonates
• Female
• Humans
• Mice
• Mice, Nude
• Picolines (chemistry, pharmacology)
• Transplantation, Heterologous