EVALUATION OF THE EFFECTS OF NEWLY SYNTHESIZED METALLOPHTHALOCYANINES ON BREAST CANCER CELL LINES WITH PHOTODYNAMIC THERAPY


Bostancı H. E. , Bilgiçli A. T. , Güzel E., Günsel A., Hepokur C., Çimen B., ...More

DALTON TRANSACTIONS, vol.1, pp.1-20, 2022 (Peer-Reviewed Journal)

  • Publication Type: Article / Article
  • Volume: 1
  • Publication Date: 2022
  • Doi Number: 10.1039/d2dt01912d
  • Journal Name: DALTON TRANSACTIONS
  • Journal Indexes: Science Citation Index Expanded
  • Page Numbers: pp.1-20

Abstract

In this study, the new phthalonitrile derivative 3-(4-(3-oxobutyl)phenoxy)phthalonitrile (1) and its non-peripheral metallophthalocyanine derivatives [Zinc(II) (2), Copper(II) (3), Cobalt (II) (4), Manganese (III) (5), Gallium (III) (6), and Indium (III) (7)] were synthesized. The synthesized new compounds were characterized by standard spectroscopic methods such as FT-IR, 1H NMR, UV-Vis, fluorescence spectroscopies, and MALDI-TOF spectrometry. Aggregation behaviors of novel metallophthalocyanines were investigated by UV-Vis spectroscopy. The effect of pH change on electronic and emission spectra of newly synthesized phthalocyanine derivatives was performed in THF media. The electronic spectra of new type Zinc (II) (2), Copper (II) (3), and Cobalt (II) (4) metallophthalocyanines exhibited bahthochromic shifts in acidic pH values due to occur of monoprotonated forms. Suprisingly, the same effect was not observed for Manganese (III) (5) and Indium (III) (7). On the other hand, the Gallium (III) (6) showed a slight red-shifted band with the addition of HCl to the medium. Also, it was determined that the synthesized Zinc (II) (2) and Gallium (III) (6) phthalocyanines had a selective phototoxic effect on the MCF-7 breast cancer cell line compared to the MCF-10a healthy breast cell line. IC50 values of Zinc (II) (2) and Gallium (III) (6) phthalocyanines were performed for MCF-7 and MCF-10a cell lines. IC50 values of MCF-7 for compounds 2 and 6 are found that 1.721 ± 0.4 µg/mL and 7.406 ± 0.32 µg/mL, respectively. IC50 values of MCF-10a for compounds 2 and 6 are found that 48.90 ± 0.69 µg/mL and 14.77 ± 1.09 µg/mL, respectively. In the LDH (Lactate Dehydrogenase)-ELISA study, LDH levels formed on a cell basis after the application were measured, and it was observed that the cells were directed towards apoptosis. In addition, it was observed that cancer cells undergo more apoptosis than healthy cells as a result of this application with cell-cycle and dead cell kits performed by flow cytometry. This research shows that non-peripheral substituted gallium and zinc phthalocyanine derivatives (2 and 6) can be suitable photosensitizers for the photodynamic treatment of breast cancers.