Synthesis of Novel Lipophilic Polyamines via Ugi Reaction and Evaluation of Their Anticancer Activity

通过Ugi反应合成新型亲脂性多胺及其抗癌活性评价

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作者:Artemiy Nichugovskiy, Varvara Maksimova, Ekaterina Trapeznikova, Elizaveta Eshtukova-Shcheglova, Igor Ivanov, Marianna Yakubovskaya, Kirill Kirsanov, Dmitry Cheshkov, Gian Cesare Tron, Mikhail Maslov

Abstract

Natural polyamines (PAs) are involved in the processes of proliferation and differentiation of cancer cells. Lipophilic synthetic polyamines (LPAs) induce the cell death of various cancer cell lines. In the current paper, we have demonstrated a new method for synthesis of LPAs via the multicomponent Ugi reaction and subsequent reduction of amide groups by PhSiH3. The anticancer activity of the obtained compounds was evaluated in the A-549, MCF7, and HCT116 cancer cell lines. For the first time, it was shown that the anticancer activity of LPAs with piperazine fragments is comparable with that of aliphatic LPAs. The presence of a diglyceride fragment in the structure of LPAs appears to be a key factor for the manifestation of high anticancer activity. The findings of the study strongly support further research in the field of LPAs and their derivatives.

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