Mitochondriotropic agents conjugated with NSAIDs through metal ions against breast cancer cells

Christina N Banti; Angeliki A Piperoudi; Catherine P Raptopoulou; Vassilis Psycharis; Constantinos M Athanassopoulos; Sotiris K Hadjikakou

doi:10.1016/j.jinorgbio.2023.112420

Mitochondriotropic agents conjugated with NSAIDs through metal ions against breast cancer cells

J Inorg Biochem. 2024 Jan:250:112420. doi: 10.1016/j.jinorgbio.2023.112420. Epub 2023 Oct 24.

Authors

Christina N Banti¹, Angeliki A Piperoudi², Catherine P Raptopoulou³, Vassilis Psycharis³, Constantinos M Athanassopoulos⁴, Sotiris K Hadjikakou⁵

Affiliations

¹ Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, Ioannina 45110, Greece. Electronic address: cbanti@uoi.gr.
² Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, Ioannina 45110, Greece.
³ NCSR "Demokritos", Institute of Nanoscience and Nanotechnology, A. Paraskevi Attikis, Greece.
⁴ Department of Chemistry, University of Patras, Patras, Greece.
⁵ Inorganic and Analytical Chemistry, Department of Chemistry, University of Ioannina, Ioannina 45110, Greece; University Research Centre of Ioannina (URCI), Institute of Materials Science and Computing, Ioannina, Greece. Electronic address: shadjika@uoi.gr.

PMID: 37918185
DOI: 10.1016/j.jinorgbio.2023.112420

Abstract

Two copper(I) polymorphs of formula [Cu(SALH)(TPP)₃] (1a and 1b) were prepared by the conjugation of the Non-Steroidal Anti-Inflammatory Drug (NSAID) salicylic acid (SALH₂) with the mitochondriotropic agent triphenylphosphine (TPP) via metal ion. For comparison, the isomorph [Ag(SALH)(TPP)₃] (2) was prepared. The conjugates 1a, 1b and 2 were characterized by melting point (m.p.), Attenuated total reflection Fourier-transform infrared (ATR-FTIR) spectroscopy, Ultraviolet-Visible (UV-Vis) spectroscopy and nuclear magnetic resonance (¹H NMR). The crystal structures of 1a, 1b and 2 were confirmed by X-ray diffraction crystallography (XRD). The ex vivo binding affinity of 1-2 towards CT (calf thymus)-DNA was studied by UV, fluorescence, viscosity and DNA Thermal Denaturation studies. Their inhibitory activity against lipoxygenase (LOX) (an enzyme which is mainly located in the mitochondrion) was determined. The in vitro activity of 1-2 was evaluated against human breast cancer cell lines MCF-7 (hormone depended (HD)) and MDA-MB 281 (hormone independent (HI)) cells. Compounds 1-2 inhibit stronger than cisplatin the cancerous cells. The molecular mechanism of action of 1-2 was suspected by the MCF-7 cells morphology and confirmed by DNA fragmentation, Acridine Orange/Ethidium Bromide (AO/EB) Staining and mitochondrial membrane permeabilization tests.

Keywords: Antiproliferative activity; Copper(I) and silver(I) complexes; Inorganic biochemistry; Mitochondriotropic agents; NSAIDs; Polymorphs.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Anti-Inflammatory Agents, Non-Steroidal / chemistry
Anti-Inflammatory Agents, Non-Steroidal / pharmacology
Antineoplastic Agents* / chemistry
Antineoplastic Agents* / pharmacology
Breast Neoplasms* / drug therapy
Coordination Complexes* / chemistry
Coordination Complexes* / pharmacology
Copper
DNA / chemistry
Female
Hormones
Humans
Silver / chemistry

Substances

Anti-Inflammatory Agents, Non-Steroidal
Silver
DNA
Hormones
Antineoplastic Agents
Coordination Complexes
Copper