Comparative inhibition of prostate cell invasion by conformationally flexible and constrained bis(2,6-dioxopiperazine)s

  • Authors:
    • M Wientjes
    • R Stephens
    • A KoolemansBeynen
    • S Eturi
    • D Witiak
  • View Affiliations

  • Published online on: November 1, 1997     https://doi.org/10.3892/or.4.6.1135
  • Pages: 1135-1139
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Abstract

Inhibition of the migration of human prostate cancer PC-3 cells by a series of 18 conformationally flexible and constrained bis(2,6-dioxopiperazine)s including selected bis(morpholinomethyl) derivatives was investigated in vitro using the Matrigel invasion assay. The anti-invasion effects were compared to the cytotoxic effects of these experimental drugs. The parent conformationally mobile ICRF-159 (razoxane) and its dextrorotatory isomer ICRF-187 (dexrazoxane) inhibited invasion at concentrations that were at least 19-fold lower than their cytotoxic concentrations. This indicates that the anti-invasion effect was achieved independent of cytotoxicity. Seven conformationally constrained compounds were found to have no appreciable anti-invasive activity. Generally, the morpholinomethyl pro-drug derivatives of seven of the dioxopiperazines, exhibited either anti-invasive or cytotoxic activities that were reduced or unchanged relative to the parent molecules. In summary, certain bis(2,6-dioxopiperazine)s exhibit a promising and selective anti-invasion effect in human prostate cells. This activity seems to require a flexible linker allowing for multiple conformational possibilities of the dioxopiperazine rings.

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November 1997
Volume 4 Issue 6

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Wientjes M, Stephens R, KoolemansBeynen A, Eturi S and Witiak D: Comparative inhibition of prostate cell invasion by conformationally flexible and constrained bis(2,6-dioxopiperazine)s. Oncol Rep 4: 1135-1139, 1997.
APA
Wientjes, M., Stephens, R., KoolemansBeynen, A., Eturi, S., & Witiak, D. (1997). Comparative inhibition of prostate cell invasion by conformationally flexible and constrained bis(2,6-dioxopiperazine)s. Oncology Reports, 4, 1135-1139. https://doi.org/10.3892/or.4.6.1135
MLA
Wientjes, M., Stephens, R., KoolemansBeynen, A., Eturi, S., Witiak, D."Comparative inhibition of prostate cell invasion by conformationally flexible and constrained bis(2,6-dioxopiperazine)s". Oncology Reports 4.6 (1997): 1135-1139.
Chicago
Wientjes, M., Stephens, R., KoolemansBeynen, A., Eturi, S., Witiak, D."Comparative inhibition of prostate cell invasion by conformationally flexible and constrained bis(2,6-dioxopiperazine)s". Oncology Reports 4, no. 6 (1997): 1135-1139. https://doi.org/10.3892/or.4.6.1135