Evaluation cytotoxic activity of Zn(II) phthalocyanine on cancer cells and molecular docking studies

Year 2024, , 115 - 128, 20.12.2024

Uğur Uzuner , Selcen Çelik Uzuner , İsmail Hakkı Kaya , Çağla Akkol , Meryem Yılmaz , Ece Tuğba Saka

https://doi.org/10.51435/turkjac.1585651

Abstract

In this work, 2(3), 9(10), 16(17), 23(24)-tetrakis-[N-methyl-(1-benzylpiperidin-4-yl)oxy) phthalocyaninato]zinc(II) iodide was synthesized and its agregation behavior was investigated in different solvents and concentrations. After the cytotoxic effect of 2(3), 9(10), 16(17), 23(24)-tetrakis-[N-methyl-(1-benzylpiperidin-4-yl)oxy)phthalocyaninato]zinc(II) iodide was tested, the treatment at certain conditions with phthalocyanine was resulted in a significant cell death (around 30%) in AR42J pancreatic cancer cells and Sol8 normal muscle cells but same results were not observed in MDA-MD-231metastatic breast cancer cells.To evaluate mitochondrial membrane potential (MMP), Mitotracker Red staining was performed and the treatment at certain conditions with 2(3), 9(10), 16(17), 23(24)-tetrakis-[N-methyl-(1-benzylpiperidin-4-yl)oxy)phthalocyaninato]zinc(II) iodide was resulted in a significant decrease in mitochondrial membrane potential (represented by Δψm) in MDA-MB-231 cells, but the same situation was not observed inother cells. In silicoanalyseswere performed for intracellular target prediction of 2(3), 9(10), 16(17), 23(24)-tetrakis-[N-methyl-(1-benzylpiperidin-4-yl)oxy)phthalocyaninato]zinc(II) iodide and we found that it has inhibitory effects on Sigmar1 protein and Adinopection receptors 1-2 with the lowest binding energiesas–13.07kcal/mol, –10.93kcal/moland –9.49 kcal/mol, respectively. Sigmar1 is an integral protein localized in mitochondrial membraneswhile communication between mitochondria and endoplasmic reticulum and Adiponectin receptors are known to be associated with mitochondrial function. These results suggest that 2(3), 9(10), 16(17), 23(24)-tetrakis-[N-methyl-(1-benzylpiperidin-4-yl)oxy)phthalocyaninato]zinc(II) iodide has a cytotoxic potential on cancer cells and inhibited MMP in breast cancer cells only.

Keywords

zinc (II) phthalocyanine, aggregation, water soluble, metastatic breast cancer, mitochondrial membrane potential, molecular docking.

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