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.
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This investigation was supported by USPHS Grant CA34200 from the National Cancer Institute, Bethesda, MD.
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Struck, R.F., Waud, W.R. Thiolo-, thiono- and dithiocarbonate and thiocarbamate derivatives of demethylpenclomedine as novel anticancer agents. Cancer Chemother Pharmacol 57, 180–184 (2006). https://doi.org/10.1007/s00280-005-0031-6
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DOI: https://doi.org/10.1007/s00280-005-0031-6