Effects of electroporation on anticancer activity of 5-FU and newly synthesized zinc(II) complex in chemotherapy-resistance human brain tumor cells.

Mehmet Eşref Alkış,Yusuf Alan,Nevin Turan,Kenan Buldurun,Sevgi Irtegun Kandemir

doi:10.1007/s12032-021-01579-7

Mehmet Eşref Alkış, Yusuf Alan + Show 3 more

Open Access

https://doi.org/10.1007/s12032-021-01579-7

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Abstract

Zn(II) complex of Schiff base derived from the condensation of 4-aminopyrimidine-2(1H)-one with salicylaldehyde was prepared and characterized by various physico-chemical and spectral methods for structure determination. The cytotoxic activity of the Zn(II) complex was investigated in comparison with 5-fluorouracil (5-FU) against two different human brain tumor cell lines (T98G and U118), while primer human dermal fibroblast cells (HDF) was used as control for biocompatibility. Then, the effectiveness of electroporation (EP) on cytotoxic activities of these compounds has been examined. The cytotoxicities of the 5-FU and new Zn(II) complex, alone or in combination with electroporation, were determined by MTT assay. The Zn(II) complex showed good cytotoxicity against T98G and U118 brain tumor cell lines with IC50 = 282.47 and 297.91μM respectively, while it was safe on HDF healthy cells with IC50 = 826.72μM. The 5-FU exhibited less cytotoxicity compared to the Zn(II) complex against T98G (IC50 = 382.35μM) and U118 (IC50 = 396.56μM) tumor cell lines. The combined application of Zn (II) + EP decreased the IC50 value by 5.96-fold in T98G cells and 4.76-fold in U118 cells. EP showed a similar effect in its combined application with 5-FU, resulting in a decrease of the IC50 value of 4.22-fold in the T98G cells and 3.84-fold in the U118 cells. In a conclusion, the Zn(II) complex exhibited an anticancer potential against both brain tumor cell lines (T98G and U118) and EP greatly increased the cytotoxicity of Zn(II) complex and 5-FU on these chemotherapy-resistant cells.

Highlights

Schiff bases are known as compounds containing the azomethine functionality (-HC=N-)
The cytotoxic activity of the Zn(II) complex was investigated in comparison with 5-fluorouracil (5-FU) against two different human brain tumor cell lines (T98G and U118), while primer human dermal fibroblast cells (HDF) was used as control for biocompatibility
The infrared spectra of the prepared Schiff base-Zn(II) complex were measured in KBr disc and significant FT-IR spectral assignments were shown in the experimental section

Summary

Introduction

Schiff bases are known as compounds containing the azomethine functionality (-HC=N-). Schiff bases are good α-donors and very excellent π-acid ligands, as these could accept the electronic density into empty π*-antibonding molecular orbitals of azomethine group from metal possessing low oxidation states. Schiff bases are considered to be a versatile pharmacophore for the drug design and development of numerous bioactive compounds. They serve a vital role in industrial, herbicidal, antibacterial, antifungal and anticancer applications, especially when complexed with transition metals [1,2,3,4]. It is well known that various Schiff base complexes of Cu(II), Zn(II), and Ni(II) are used as antiinflammatory, anti-bacterial, anti-diabetic, chemo-sensors, anti-cancer, antipyretic and anti-HIV [5,6]

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