Cancer Chemotherapy and Pharmacology

, Volume 14, Issue 2, pp 160–164 | Cite as

Comparative cytotoxicities of various morpholinyl anthracyclines

  • D. G. Streeter
  • D. L. Taylor
  • E. M. Acton
  • J. H. Peters
Original Articles In vitro Cytotoxicity
Received:
Accepted:

Summary

A series of quinone- and sugar-modified analogs of adriamycin have been tested for growth inhibition of adriamycin-sensitive (P388/S) and -resistant (P388/ADR) sublines of P388 murine leukemia cells in vitro. P388/ADR is less resistant to analogs of adriamycin containing either a 3′-deamino-3′-(4″-morpholinyl) group, MRA; or a-(3″-cyano-4″-morpholinyl) group, MRA-CN, than to adriamycin. However, MRA-CN was the most potent growth inhibitor of either subline. This potency is reduced by either modification of the quinone unit with a 5-imino substituent or restriction of the cyano-morpholinyl ring by an oxygen bridge to the daunosamine sugar. The calcium antagonist verapamil substantially increases the cytotoxicity of adriamycin to P388/ADR but has no appreciable effect on the cytotoxicity of either MRA or MRA-CN. The results suggest that increased uptake and retention by both MRA and MRA-CN may contribute to their increased cytotoxicity, but that the intense potency of the cyano-morpholinyl analogs must be due to other unique properties of these compounds.

Keywords

Leukemia Quinone Verapamil Leukemia Cell Calcium Antagonist 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.
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Copyright information

© Springer-Verlag 1985

Authors and Affiliations

  • D. G. Streeter
    • 1
  • D. L. Taylor
    • 1
  • E. M. Acton
    • 1
  • J. H. Peters
    • 1
  1. 1.SRI InternationalMenlo ParkUSA

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