Chimeric Amides of Substituted Allyl- and Phenylcarboxylic Acids with Pharmacophoric Moieties of Aromatic and Heteroaromatic Rings as Potential Multitarget Protein Kinase Inhibitors: Design, Synthesis, Evaluation of Antitumor Activity, and In Silico Analysis
摘要
Objective: This study aims to synthesize and evaluate the antitumor efficacy of a series of designed chimeric amides (10–14, 16, 19, 21, 25–27, 28, 30) containing various combinations of nitrogen-based heterocycles, which are the key pharmacophores of many antitumor drugs with different mechanisms of action. Methods: The designed amides were synthesized and characterized using spectroscopic techniques. The antitumor activity of all these compounds against tumor cell lines K562 (chronic myeloid leukemia), HL-60 (acute promyelocytic leukemia), and HeLa (cervical carcinoma) was evaluated in vitro in terms of the half-maximal inhibitory concentration (IC50). Results and Discussion: As a result, five lead compounds, amides (10, 11, 21, 27, 30), active against the above cell lines, were identified, followed by in silico analysis of their pharmacological properties and prediction of the most probable mechanism of their action against myeloid blood cells K562. Conclusions: In light of the data obtained, the identified compounds provide promising basic structures for the design of novel orally active antitumor agents, multitarget protein kinase inhibitors.