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Additional functionality for plecstatin-1-analogous anticancer Ru(η6-p-cymene)Cl complexes.

Shahid Iqbal1, Adnan Ashraf2, Anne Dill3

  • 1School of Chemical Sciences, The University of Auckland, Private Bag 92019, Auckland 1142, New Zealand; Institute of Chemistry, University of Sargodha, Sargodha 40100, Pakistan.

Journal of Inorganic Biochemistry
|December 11, 2025
PubMed
Summary

Researchers conjugated amino acids to pyridine-2-carbothioamides (PCAs) and formed ruthenium(II) organometallics. Compound 4a demonstrated moderate antiproliferative activity against non-small cell lung cancer cells.

Keywords:
Amino acid conjugationAntiproliferative activityN,S-coordinating ligandsPyridinecarbothioamide complexesRuthenium arene complexesStability studies

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Area of Science:

  • Organometallic Chemistry
  • Medicinal Chemistry
  • Cancer Research

Background:

  • Ligand modification enhances organometallic compound bioactivity.
  • Amino acid conjugation to pyridine-2-carbothioamides (PCAs) is a strategy to alter biological action.

Purpose of the Study:

  • To synthesize and characterize novel Ruthenium(II) organometallic compounds.
  • To evaluate the in vitro antiproliferative activity of these compounds against various cancer cell lines.

Main Methods:

  • Synthesis of amino acid-conjugated PCAs and their Ru(II)(cym)Cl organometallics.
  • Characterization using mass spectrometry, NMR spectroscopy, and elemental analysis.
  • In vitro antiproliferative assays against NCI-H460, SiHA, HCT116, and SW480 cell lines.

Main Results:

  • Complex 4a exhibited moderate antiproliferative activity against NCI-H460 cells with an IC50 of 35 μM.
  • Complex 4a showed higher potency than its parent PCA ligand (4) and the clinical Ru complex KP1339 in NCI-H460 cells.
  • Complexes 1a-3a displayed no significant antiproliferative activity.

Conclusions:

  • The novel organoruthenium compound 4a shows promising antiproliferative effects against non-small cell lung cancer.
  • Amino acid conjugation to PCAs can lead to potent Ru(II) anticancer agents.
  • Further investigation of compound 4a is warranted for its potential therapeutic applications.