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4,7-二氢-6-硝基氮杂并[1,5-a]嘧啶类化合物的 CK2 抑制作用和抗肿瘤活性。

CK2 Inhibition and Antitumor Activity of 4,7-Dihydro-6-nitroazolo[1,5-a]pyrimidines.

机构信息

Department of Organic and Biomolecular Chemistry, Ural Federal University, Mira St. 19, 620002 Ekaterinburg, Russia.

Department of Pharmacology & Bioinformatics, Scientific Center for Innovative Drugs, Volgograd State Medical University, 400131 Volgograd, Russia.

出版信息

Molecules. 2022 Aug 17;27(16):5239. doi: 10.3390/molecules27165239.

DOI:10.3390/molecules27165239
PMID:36014483
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC9415015/
Abstract

Today, cancer is one of the most widespread and dangerous human diseases with a high mortality rate. Nevertheless, the search and application of new low-toxic and effective drugs, combined with the timely diagnosis of diseases, makes it possible to cure most types of tumors at an early stage. In this work, the range of new polysubstituted 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines was extended. The structure of all the obtained compounds was confirmed by the data of H, C NMR spectroscopy, IR spectroscopy, and elemental analysis. These compounds were evaluated against human recombinant CK2 using the ADP-GloTM assay. In addition, the IC parameters were calculated based on the results of the MTT test against glioblastoma (A-172), embryonic rhabdomyosarcoma (Rd), osteosarcoma (Hos), and human embryonic kidney (Hek-293) cells. Compounds , , and showed a CK2 inhibitory activity close to the reference molecule (staurosporine). The most potential compound in the MTT test was with an IC from 13 to 27 µM. Thus, our results demonstrate that 4,7-dihydro-6-nitroazolo[1,5-a]pyrimidines are promising for further investigation of their antitumor properties.

摘要

如今，癌症是一种最普遍且危险的人类疾病，具有很高的死亡率。然而，新的低毒有效药物的研究和应用，结合疾病的及时诊断，使得在早期治愈大多数类型的肿瘤成为可能。在这项工作中，扩展了新的多取代 4,7-二氢-6-硝基氮杂并[1,5-a]嘧啶的范围。所有获得的化合物的结构均通过 H、C NMR 光谱、IR 光谱和元素分析数据得到证实。这些化合物使用 ADP-GloTM 测定法针对人重组 CK2 进行了评估。此外，根据对神经胶质瘤（A-172）、胚胎横纹肌肉瘤（Rd）、骨肉瘤（Hos）和人胚肾（Hek-293）细胞的 MTT 试验结果计算了 IC 参数。化合物 、 和 对 CK2 的抑制活性接近参考分子（星形孢菌素）。在 MTT 试验中最有潜力的化合物是 ，其 IC 为 13 到 27 µM。因此，我们的结果表明 4,7-二氢-6-硝基氮杂并[1,5-a]嘧啶具有进一步研究其抗肿瘤特性的潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/ba46a5163575/molecules-27-05239-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/638f93443d5a/molecules-27-05239-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/13f4cdef5646/molecules-27-05239-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/e2f24ecfd0b5/molecules-27-05239-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/5c9be9569df5/molecules-27-05239-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/ba46a5163575/molecules-27-05239-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/638f93443d5a/molecules-27-05239-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/13f4cdef5646/molecules-27-05239-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/e2f24ecfd0b5/molecules-27-05239-sch001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/5c9be9569df5/molecules-27-05239-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/03dc/9415015/ba46a5163575/molecules-27-05239-g004.jpg

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