Design, Synthesis, and Anti-Cancer Evaluation of Novel Water-Soluble Copper(I) Complexes Bearing Terpyridine and PTA Ligands

Molecules. 2024 Feb 21;29(5):945. doi: 10.3390/molecules29050945.

Abstract

This study presents a simple and energy-efficient self-assembly LAG synthetic method for novel water-soluble copper(I) complexes [Cu(terpy)(PTA)][PF6] (1) and [Cu(terpy)(PTA)2][PF6] (2). They were characterized by FT-IR, 1H, and 31P{1H} NMR spectroscopy, elemental analysis, and single-crystal/powder X-ray diffraction (for 2). The X-ray analysis of compound 2 indicates a bidentate coordination mode of terpyridine to the metal center. Variable-temperature NMR tests indicate dynamic properties for terpyridine in the case of both compounds, as well as for the PTA ligands in the case of 2. Additionally, compounds 1 and 2 exhibit interesting cytotoxic activity, which was tested on normal human dermal fibroblasts (NHDFs), human lung carcinoma (A549), human breast adenocarcinoma (MCF-7), and human cervix carcinoma (HeLa) established cell lines. In comparison to the other tested compounds, complexes 1 and 2 seem to have significantly lower IC50 values against cancer cells (A549, HeLa, MCF-7), indicating their potential as prospective anticancer agents. Moreover, both compounds show no significant toxicity towards normal skin cells (NHDFs), suggesting a certain selectivity in their action on cancer cells. Cisplatin as a reference compound also exhibited considerable cytotoxicity against cancer cells but with a low level of selectivity, which could lead to unwanted effects on normal cells. Remarkably, compounds 1 and 2 exhibit up to 30 times the cytotoxic activity of cisplatin, with a six-fold lower toxicity to normal cells. They also interact strongly with human serum albumin, suggesting potential therapeutic applications. Overall, these compounds hold significant promise as potential chemotherapeutic agents.

Keywords: MTT test; NMR test; cytotoxicity; spectroscopy; water-soluble copper(I) complexes.

MeSH terms

  • Adamantane / analogs & derivatives*
  • Antineoplastic Agents* / pharmacology
  • Carcinoma*
  • Cell Line, Tumor
  • Cisplatin / pharmacology
  • Coordination Complexes* / chemistry
  • Copper / chemistry
  • Female
  • Humans
  • Ligands
  • Organophosphorus Compounds*
  • Prospective Studies
  • Spectroscopy, Fourier Transform Infrared
  • Water

Substances

  • Cisplatin
  • Copper
  • Water
  • Coordination Complexes
  • Antineoplastic Agents
  • 1,3,5-triaza-7-phosphaadamantane
  • Ligands
  • Adamantane
  • Organophosphorus Compounds