Synthesis, characterization, and pharmacological evaluation of new imatinib analogues as antiproliferative agents

Abstract

Cancer is the second cause of death after the cardiovascular disease. There are many target receptors for a drug that acts as an anticancer. One of these targets is the tyrosine kinase which is considered one of the most platforms for cancer therapeutics in the recent years. For instance, imatinib is known as a prototype that acts by inhibiting tyrosine kinase receptors. Nevertheless, after one year of receiving imatinib, many patients developed resistance to treatment. Hence, there is an unmet necessity to develop new compounds in an attempt to tackle the resistance issues. In the current work, new imatinib analogues were synthesized with approved attributes. The structures were characterized and confirmed by spectral tools (FTIR,1HNMR, and 13CNMR). Furthermore, the physicochemical properties were acquired with variant reliable techniques (melting point by DSC, Retention factor by TLC, and material description alongside the physical appearance). Moreover, the cytotoxicity of the compound against human lung cancer cell line (A549) was investigated by viability test with an MTT reagent. As a result, compound IIX possesses IC50 =0.623 µM which is three-fold more potent than the reference drug, imatinib (IC50=2.479 µM).