Antiproliferative Activity of the New Analogues of Acridine/Acridone With Oligopeptide Derivatives and Molecular Docking With EGFR and Src Kinase

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.