Cytotoxic and Apoptotic Effects of the New Derivatives of Quinazoline Family on K562 Cells, Chronic Myelogenous Leukemia

Chronic Myelogenous Leukemia (CML) is a clonal pluripotent hematopoietic stem cell disorder which increases the number of abnormal white blood cells. Recently, Quinazoline derivatives have been considered for cancer treatment. The objective of this study was to determine the cytotoxicity and apoptosis effects of the new Quinazoline derivatives on K562 cell line, CML. Methods and Materials: The colorimetric MTT test was used to evaluate cytotoxicity of these compounds. The K562 cells were seeded in 96-well plates at 2×104 cells/well and treated with various concentrations (100-300μM) of the Quinazoline compounds (4t-CHQ، 4-CHQ and 4-CPQ) for 24, 48 and 72 h. Inverted and fluorescent microscopy were used to evaluate the morphological changes and apoptosis. Apoptosis was also confirmed by DNA fragmentation assay. The results showed that the Quinazoline compounds cause cell death in a dose- and time-dependent manner. 4t-CHQ، 4-CHQ and 4-CPQ were found to be highly active cell proliferation inhibitor with IC50 values of 200, 280 and 280 μM, respectively. Given that the basic structures of these compounds, the compound with a reactive group showed stronger cytotoxic activity. The results indicated that structure and function of these compounds are related to each other. Fluorescent microscopy and DNA fragmentation assay was confirmed apoptosis cell death in K562 cells after 48 h of treatment with the compounds. Base on these results, the new Quinazoline derivatives can be proposed as effective agents for more investigation in the field of chemotherapy.