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Updated: Oct 3, 2026

Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents
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Amide Coupling Reaction for the Synthesis of Bispyridine-based Ligands and Their Complexation to Platinum as Dinuclear Anticancer Agents

Published on: May 28, 2014

Liver organotropism and biotransformation of a novel platinum-ursodeoxycholate derivative, Bamet-UD2, with enhanced

M G Larena1, M C Martinez-Diez, M J Monte

  • 1Department of Physiology and Pharmacology, School of Pharmacy, University of Salamanca, 37007-Salamanca, Spain.

Journal of Drug Targeting
|November 8, 2001
PubMed
Abstract

Insights

Bamet-UD2, a novel cisplatin-ursodeoxycholate derivative, shows potent anticancer activity with enhanced liver targeting and reduced toxicity compared to cisplatin. This compound demonstrates significant potential for cancer treatment by improving drug delivery and safety profiles.

Area of Science:

  • Medicinal Chemistry
  • Pharmacology
  • Hepatology

Background:

  • Novel bile acid derivatives with cytostatic and virostatic activity have been synthesized.
  • Two compounds, Bamet-D3 and Bamet-UD2, exhibit enhanced DNA-reactivity.
  • Bamet-D3 links glycocholic acid to platinum via a glycine-polyamine spacer.
  • Bamet-UD2 directly binds cisplatin to ursodeoxycholic acid moieties.

Purpose of the Study:

  • Investigate the liver organotropism and biotransformation of Bamet-D3 and Bamet-UD2.
  • Evaluate the anticancer efficacy and toxicity profiles of these novel platinum derivatives.

Main Methods:

  • In vitro studies using rat hepatocytes for drug uptake and toxicity.
  • In vivo pharmacokinetic and biodistribution studies in rats following intravenous administration.
  • HPLC analysis of bile for liver biotransformation and atomic absorption spectroscopy for total platinum.
  • Antitumor activity assessment in Nude mice bearing Hepa 1-6 hepatoma cells.

Main Results:

  • Bamet-UD2 showed significantly higher hepatocyte uptake and in vitro toxicity compared to Bamet-D3 and cisplatin.
  • In vivo, Bamet-UD2 exhibited no toxicity, high bile output with minimal biotransformation, and marked liver-vectoriality.
  • Bamet-UD2 demonstrated potent antitumor activity, significantly prolonging survival time in mice, with reduced kidney excretion compared to cisplatin.

Conclusions:

  • Bamet-UD2 is a promising cisplatin-ursodeoxycholate derivative with strong antitumor efficacy.
  • It possesses marked hepatobiliary organotropism and a favorable safety profile compared to cisplatin.
  • Bamet-UD2 represents a potential advancement in cancer therapy due to its targeted delivery and reduced side effects.

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