Antiproliferative Effects of Fluorine Substitute 3,5-di-<i>tert</i>-butylphenol Bearing Schiff Bases Using CFSE-Based Cell Proliferation Assay

Abstract

The determination of antiproliferative properties of compounds on tumour cells is important for assessment of their efficacy in cancer treatment. CFSElabelled K562 cells were incubated with doxorubicin and ortho-or para-fluorosubstitute Schiff bases (compounds 1 and 2 respectively). CFSE intensities were analysed using flow cytometry. K562 cells treated with doxorubicin resulted in homogeneous high intensity fluorescence after 96 h of incubation. Schiff bases exhibited antiproliferative effects, but lower than doxorubicin. Our results reveal that CFSE assay can be used for determining in vitro antiproliferative features of anticancer drugs and/or compounds from herbal or chemical sources.Keywords: Cancer, CFSE, doxorubicin.THERE have been many attempts to explore new chemotherapeutic agents from chemical and herbal sources worldwide. The determination of cytotoxic and antiproliferative effects of organic compounds has crucial importance in the evaluation of anticancer potential 1 . Although there are some precise methods such as 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) or ATP-based tumour chemosensitivity (ATP-TCA) assays to determine the cytotoxic capacity of herbal or chemical compounds [2][3][4] , there are no precise methods to quantitively determine the antiproliferative effects of compounds or assess multiparameters in anticancer research.The carboxyfluorescein diacetate succinimidyl ester (CFSE) assay is currently used to determine cell proliferation with flow cytometry 5 . The CFSE assay is based on general protein labelling by CFSE in which an aminoreactive dye forms stable covalent bonds with cell proteins [6][7][8] . An equal and progressive division of CFSE fluorescence occurs within daughter cells after each cellular division which suggests in vitro cell proliferation 9 . This fluorescent cell tracking assay can be a powerful tool to study the antiproliferative effects of anticancer drugs or herbal and chemical compounds in vitro.Schiff bases derived from an amine and carboxylic compounds belong to a class of ligands involved in the coordination of metal ions via azomethine nitrogen 10 . The C=N linkage is crucial for biological activity in azomethine derivatives, and it was reported that various azomethines are characterized to have roles against bacteria, fungi and cancer11 . An appreciable amount of Schiff-base complexes are quite successful models of biological compounds 12 . Fluorinated compounds have recently drawn attention due to their therapeutic applications in various medical areas 13 . 5-Fluorouracil (5-FU), a synthetic flourinated antineoplastic agent, is being used as an antimetabolite to treat malignancies such as breast, head, neck and gastrointestinal malignancies 14 . 5-FU irreversibly inhibiting thymidylate synthase can cause the death of rapidly dividing cancerous cells 15 . Tamoxifen is another fluorinated compound used for treatment of hormonedependent breast cancer as an oestrogen antagonist 16 . Gemcitabine is another fluorinated compound used in the...

Investigation of anticancer and antimicrobial properties of fluorinated salicylaldimine’s Florlu salisilaldiminlerin antikanser ve antimikrobiyal özelliklerinin araştırılması

“…In a recent study, aminophenylhydrazine SB compounds were tested for their antiproliferative capacity on A549 cells and showed that those containing two fluorine atoms had the strongest antiproliferative effect compared to five fluorine atoms [42]. Another study with SB compounds carrying fluorine atoms in the ortho and para positions showed that the antiproliferative effects of the compounds on K562 cells were lower than that of DOX [43]. In our study, although the lowest PI value among SB ligands was obtained with 5 fluorinated compounds, this antiproliferative capacity lagged behind DOX, which is the standard chemotherapeutic drug.…”