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Acyl derivatives of demethylpenclomedine, an antitumor-active, non-neurotoxic metabolites of penclomedine.

Publication ,  Journal Article
Struck, RF; Tiwari, A; Friedman, HS; Keir, S; Morgan, LR; Waud, WR
Published in: Cancer Chemother Pharmacol
July 2001

PURPOSE: The purpose of this investigation was to compare the antitumor activities of a series of acyl derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma metabolite of penclomedine (PEN) observed to be an active antitumor agent in vivo and non-neurotoxic in a rat model with that of DM-PEN. METHODS: Acyl derivatives were prepared from DM-PEN and evaluated in vivo against human MX-1 breast tumor xenografts implanted subcutaneously (s.c.) or intracerebrally (i.c.). Several derivatives were also evaluated against other human tumor xenografts and murine P388 leukemia cell lines. RESULTS: Several of the acyl derivatives were found to be superior to DM-PEN against MX-1, human ZR-75-1 breast tumor, human U251 CNS tumor and the P388 leukemia parent cell line and lines resistant to cyclophosphamide and carmustine. 4-Demethyl-4-methoxyacetylpenclomedine showed inferior activity to current clinical brain tumor drugs against a glioma cell line, superior activity to temozolomide and procarbazine against the derived mismatch repair-deficient cell line, and superior activity to cyclophosphamide and carmustine but inferior activity to temozolomide against two ependymoma cell lines, all of which were implanted s.c. CONCLUSION: Proposed mechanisms of activation and action of DM-PEN and the acyl derivatives support the potential clinical superiority of the acyl derivatives.

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Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

July 2001

Volume

48

Issue

1

Start / End Page

47 / 52

Location

Germany

Related Subject Headings

  • Transplantation, Heterologous
  • Structure-Activity Relationship
  • Picolines
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice
  • Humans
  • Brain Neoplasms
  • Antineoplastic Agents
  • Animals
 

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Struck, R. F., Tiwari, A., Friedman, H. S., Keir, S., Morgan, L. R., & Waud, W. R. (2001). Acyl derivatives of demethylpenclomedine, an antitumor-active, non-neurotoxic metabolites of penclomedine. Cancer Chemother Pharmacol, 48(1), 47–52. https://doi.org/10.1007/s002800000255
Struck, R. F., A. Tiwari, H. S. Friedman, S. Keir, L. R. Morgan, and W. R. Waud. “Acyl derivatives of demethylpenclomedine, an antitumor-active, non-neurotoxic metabolites of penclomedine.Cancer Chemother Pharmacol 48, no. 1 (July 2001): 47–52. https://doi.org/10.1007/s002800000255.
Struck RF, Tiwari A, Friedman HS, Keir S, Morgan LR, Waud WR. Acyl derivatives of demethylpenclomedine, an antitumor-active, non-neurotoxic metabolites of penclomedine. Cancer Chemother Pharmacol. 2001 Jul;48(1):47–52.
Struck, R. F., et al. “Acyl derivatives of demethylpenclomedine, an antitumor-active, non-neurotoxic metabolites of penclomedine.Cancer Chemother Pharmacol, vol. 48, no. 1, July 2001, pp. 47–52. Pubmed, doi:10.1007/s002800000255.
Struck RF, Tiwari A, Friedman HS, Keir S, Morgan LR, Waud WR. Acyl derivatives of demethylpenclomedine, an antitumor-active, non-neurotoxic metabolites of penclomedine. Cancer Chemother Pharmacol. 2001 Jul;48(1):47–52.
Journal cover image

Published In

Cancer Chemother Pharmacol

DOI

ISSN

0344-5704

Publication Date

July 2001

Volume

48

Issue

1

Start / End Page

47 / 52

Location

Germany

Related Subject Headings

  • Transplantation, Heterologous
  • Structure-Activity Relationship
  • Picolines
  • Oncology & Carcinogenesis
  • Neoplasm Transplantation
  • Mice
  • Humans
  • Brain Neoplasms
  • Antineoplastic Agents
  • Animals