Thiolo-, thiono- and dithiocarbonate and thiocarbamate derivatives of demethylpenclomedine as novel anticancer agents |
| |
Authors: | Robert F Struck William R Waud |
| |
Institution: | (1) Southern Research Institute, 2000 Ninth Avenue South, P.O. Box 55305, Birmingham, Alabama 35255-5305, USA |
| |
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.
This investigation was supported by USPHS Grant CA34200 from the National Cancer Institute, Bethesda, MD. |
| |
Keywords: | Penclomedine 4-demethylpenclomedine Antitumor evaluation in vivo Human tumor xenografts |
本文献已被 PubMed SpringerLink 等数据库收录! |
|