Antitumor activity of l-OHP in mice

Cancer Letters
|June 1, 1985
PubMed

Insights

The platinum complex l-OHP shows promise as an anti-cancer drug, demonstrating superior activity against certain murine leukemias and lymphomas compared to CDDP, with reduced toxicity and no observed renal damage.

Area of Science:

  • Oncology
  • Medicinal Chemistry
  • Pharmacology

Background:

  • Diaminocyclohexane (DACH) platinum complexes exhibit anti-tumor activity.
  • Separation of the oxalato-platinum complex of trans-l-DACH isomer led to the selection of l-OHP for further study.

Purpose of the Study:

  • To evaluate the efficacy and toxicity of l-OHP in a murine tumor screening system.
  • To compare l-OHP's activity and toxicity with cis-dichlorodiamine platinum II (CDDP).

Main Methods:

  • l-OHP was administered intraperitoneally (i.p.) or intravenously (i.v.) to mice bearing L1210 leukemia, compared with CDDP.
  • l-OHP was tested at minimal effective and subtoxic doses on AkR leukemia, LGC lymphoma, glioma 26, B16 melanoma, MA 16-C mammary carcinoma, and Lewis lung carcinoma.
  • Acute toxicity (LD10 and LD50) was assessed for both drugs.

Main Results:

  • l-OHP demonstrated greater activity than CDDP against L1210 leukemia when administered i.p.
  • l-OHP significantly increased lifespan in mice with intracerebral L1210 leukemia and LGC lymphoma, where CDDP was ineffective.
  • Both drugs were active against AkR leukemia, but l-OHP exhibited lower toxicity.
  • Neither drug showed activity against tested murine solid tumors.
  • l-OHP did not cause renal toxicity, unlike CDDP.

Conclusions:

  • l-OHP is a promising anti-cancer agent with improved efficacy and reduced toxicity compared to CDDP, particularly against certain leukemias and lymphomas.
  • l-OHP warrants further investigation as a potential therapeutic agent, especially for central nervous system malignancies due to its activity against intracerebral L1210.
  • The lack of renal toxicity makes l-OHP a potentially safer alternative to CDDP.

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