通过 Ugi 反应合成新型亲脂性多胺及其抗癌活性评价。

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

机构信息

Lomonosov Institute of Fine Chemical Technologies, MIREA-Russian Technological University, 86 Vernadsky Ave., 119571 Moscow, Russia.

N.N. Blokhin National Medical Research Center of Oncology, 23 Kashirskoe Sh., 115478 Moscow, Russia.

出版信息

Molecules. 2022 Sep 21;27(19):6218. doi: 10.3390/molecules27196218.

DOI:10.3390/molecules27196218

PMID:36234753

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9572921/

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 PhSiH. 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.

摘要

天然多胺（PAs）参与癌细胞的增殖和分化过程。亲脂性合成多胺（LPAs）诱导各种癌细胞系的细胞死亡。在本文中，我们通过多组分 Ugi 反应合成了 LPAs，并通过 PhSiH 将酰胺基团还原，从而展示了一种新的方法。我们在 A-549、MCF7 和 HCT116 癌细胞系中评估了所得化合物的抗癌活性。我们首次表明，具有哌嗪片段的 LPAs 的抗癌活性与脂肪族 LPAs 的抗癌活性相当。LPAs 结构中存在二甘油酯片段似乎是表现出高抗癌活性的关键因素。该研究的结果为 LPAs 及其衍生物的进一步研究提供了有力支持。