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Novel biologically active nitro and amino substituted benzimidazo[1,2-a]quinolines

This manuscript described the synthesis and biological activity of novel nitro substituted E-2-styryl-benzimidazoles and E-2-(2-benzimidazolyl)-3-phenylacrylonitriles and nitro and amino substituted benzimidazo[1, 2-a]quinolines (4-5, 6-11, 17-20 and 21-32). All of the compounds showed significant growth inhibitory effect towards five tumor cell lines, whereby the IC50 concentrations of 11, 20, 28, 29, 30, 32 are in the low micromolar range (IC50 = 2 – 19 M). The DNA binding experiments did not show significant affinity of two selected compounds towards ds-DNA. The flow cytometry analysis of potential cell cycle perturbations after the treatment with compounds 9, 11, 25 and 29 demonstrated that all of the compounds (5 μM ≈ IC50) significantly delayed the progression through G1 phase, as demonstrated by the accumulation of cells in G1 phase, accompanied with the reduction of the cell number in the cells in S phase, which does not point to DNA damage as the main mechanism of action. Also, fluorescence microscopy study showed cytoplasmic distribution of the compounds, demonstrating that DNA is not the primary target of compounds. Thus, considerable antiproliferative effects of studied compounds are due to interactions with other biological targets within cells.

benzimidazoles ; benzimidazo[1 ; 2-a]quinolines ; antiproliferative activity ; interaction with ct-DNA ; cytometry analysis

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