| Autor: |
Struck, Robert F., Tiwari, Anita, Friedman, Henry S., Keir, Steven, Morgan, Lee, Waud, William R., Struck, R F, Tiwari, A, Friedman, H S, Keir, S, Morgan, L R, Waud, W R |
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| Zdroj: |
Cancer Chemotherapy & Pharmacology; Jul2001, Vol. 48 Issue 1, p47-52, 6p |
| Abstrakt: |
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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
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