New functionalized analogues of 1-nitroacridine/4-methyl-1-nitroacridine and 4-nitroacridone connected to tuftsin/retro-tuftsin derivatives as a potential anticancer therapeutics.
ABSTRACT
The aim of our work was to analyze new functionalized analogues of 1-nitroacridine/4-methyl-1-nitroacridine and 4-nitroacridone connected to tuftsin/retro-tuftsin derivatives as a potential anticancer therapeutics. Using the MTT assay, we have evaluated the cytotoxic activity of synthesized analogues against the Jurkat cell line and healthy donor–isolated peripheral blood mononuclear cells (PBMCs). Jurkat cells were susceptible to several of the acridine derivatives, whereas PBMCs were sensitive to two compounds only. 4-Methyl-1-nitro-acridine analogue, classified as compound 28, has exhibited the greatest anticancer potential with 4-fold higher cytotoxicity toward Jurkat cells and 12-fold lower cytotoxicity against PBMCs when compared with control therapeutics. Subsequent molecular docking analysis suggested that binding to epidermal growth factor receptor (EGFR) and proto-oncogene tyrosine-protein kinase Src molecules could be, at least partially, responsible for observed biological effects of created acridine/acridone analogues.
