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Modulating Cytotoxicity in HeLa Cells via Aromatic Ring Variation in Cu(I) Complexes.

Riya Kumari1, Swati Singh2, Shivendra Kumar Pandey1

  • 1Department of Chemistry, Banaras Hindu University, Varanasi 221005, India.

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|April 20, 2026
PubMed
Summary

New copper(I) complexes show potent anticancer activity. Increasing aromatic rings in thiosemicarbazone ligands enhanced efficacy against cervical cancer cells by inhibiting proliferation and inducing apoptosis.

Keywords:
Cu(I) complexesHeLa cellsapoptosisstructure–activity relationshipthiosemicarbazone

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Area of Science:

  • Medicinal Chemistry
  • Inorganic Chemistry
  • Cancer Biology

Background:

  • Conventional chemotherapy faces challenges, necessitating novel therapeutic agents.
  • Metal-based compounds offer unique mechanisms for cancer treatment.
  • Thiosemicarbazone ligands are versatile scaffolds for metal complex development.

Purpose of the Study:

  • To synthesize and characterize novel copper(I) complexes with varying aromatic ring densities in thiosemicarbazone ligands.
  • To evaluate the in vitro cytotoxic and antiproliferative effects of these complexes against human cervical cancer (HeLa) cells.
  • To investigate the underlying mechanisms of action, including effects on glucose metabolism, apoptosis, and neovascularization.

Main Methods:

  • Synthesis and spectroscopic characterization of four Cu(I) complexes.
  • Single-crystal X-ray diffraction for structural elucidation.
  • In vitro cytotoxicity assays (MTT, SRB), cell proliferation assays, glucose uptake measurements, lactate dehydrogenase release assays, DAPI staining, Annexin V-FITC/PI flow cytometry, and in ovo chorioallantoic membrane assays.

Main Results:

  • Copper(I) complexes (1-4) with distorted tetrahedral geometry and N,S-bidentate coordination were successfully synthesized.
  • Cytotoxic activity against HeLa cells increased with the number of aromatic rings in the thiosemicarbazone ligand, with complex 4 showing the highest potency.
  • Complex 4 demonstrated reduced glucose uptake, suppressed proliferation, induced apoptosis, and inhibited neovascularization.

Conclusions:

  • Ligand aromaticity is a critical determinant of anticancer activity in these Cu(I) complexes.
  • The observed structure-activity relationship provides valuable insights for designing novel metal-based anticancer agents.
  • These copper(I) complexes hold significant promise for further development as anticancer therapeutics.