Akademik Veri Yönetim Sistemi
MEDICINAL CHEMISTRY RESEARCH, cilt.32, sa.3, ss.475-484, 2023 (SCI-Expanded)
In this study, firstly, novel vitamin K3 analogs were synthesized by the reactions of vitamin K3 (2-methyl-1,4-naphthoquinone, also known as menadione) with some aromatic and heterocyclic ring substituted nucleophiles such as 2,4-dimethoxyaniline, 4-methoxyaniline, 4-benzylpiperidine and 1-(2-aminoethyl)piperazine in ethanol/Na2CO3, and 1-(diphenylmethyl)piperazine in chloroform/triethylamine (TEA) at room temperature. Their structures were elucidated by Fourier transform infrared spectroscopy (FT-IR), H-1 nuclear magnetic resonance (H-1 NMR), attached proton test nuclear magnetic resonance (APT-NMR) and mass spectrometry (MS). Secondly, in vitro cytotoxic effects of vitamin K3 analogs were investigated by MTT assay against three cancer cell lines (HeLa, U87 MG, and MCF-7) to evaluate their anticancer activity and a human embryonic kidney cell line (HEK-293) to check their cancer cell selectivity. One of the compounds, namely 2-((2,4-dimethoxyphenyl)amino)-3-methylnaphthalene-1,4-dione(5), was found to inhibit the growth of HeLa cervical cancer cells selectively, even better than vitamin K3, at a non-toxic concentration for healthy cells. The selectivity index of this compound for HeLa cells was calculated approximately as "3 ". Vitamin K3 was more effective against U87 MG and MCF-7 cells than its derivatives, moreover it was the only compound, which was significantly toxic to breast cancer cells, but its selectivity was poor. Furthermore, anticancer properties of piperazine derivatives of vitamin K3 were investigated by us for the first time in this study.