Chimeric Amides of Substituted Allyl- and Phenylcarboxylic Acids with Pharmacophore Fragments of Aromatic and Heteroaromatic Rings – Potential Multitarget Protein Kinase Inhibitors: Design, Synthesis, Determination of Antitumor Activity, and In Silico Analysis

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Abstract

This study aims to synthesize and evaluate the antitumor efficacy of a series designed chimeric amides (10–14, 16, 19, 21, 25–27, 28, 30) containing various combinations of nitrogen-containing heterocycles, which are the key pharmacophores of many antitumor drugs with different mechanisms of action. 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 assessed in vitro in terms of the values of half-maximal inhibitory concentration (IC50). As a result, 5 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 action against myeloid blood cells K562. In light of the data obtained, the identified compounds were shown to form promising basic structures for the design of novel orally active antitumor agents, multi-target protein kinase inhibitors.

About the authors

E. V. Koroleva

Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus

Email: evk@ichnm.by
Minsk, Belarus

Y. V. Sinyutich

Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus

Minsk, Belarus

A. L. Ermolinskaya

Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus

Minsk, Belarus

Zh. V. Ignatovich

Institute of Chemistry of New Materials of the National Academy of Sciences of Belarus

Minsk, Belarus

Y. V. Kornoushenko

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

O. V. Panibrat

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

I. M. Katok

Belarusian State Technological University

Minsk, Belarus

A. M. Andrianov

Institute of Bioorganic Chemistry of the National Academy of Sciences of Belarus

Minsk, Belarus

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