哌嗪和恶嗪连接的嘧啶作为人乳腺癌细胞中NF-κB的p65亚基结合剂的开发

Development of Piperazine- and Oxazine-Linked Pyrimidines as p65 Subunit Binders of NF-κB in Human Breast Cancer Cells.

作者信息

Ravish Akshay, Narasimhachar Bhanuprakash C, Xi Zhang, Vishwanath Divakar, Mohan Arunkumar, Gaonkar Santosh L, Chandrashekara Paduvalahippe Gowdegowda, Ahn Kwang Seok, Pandey Vijay, Lobie Peter E, Basappa Basappa

机构信息

Laboratory of Chemical Biology, Department of Studies in Organic Chemistry, University of Mysore, Mysore 570006, Karnataka, India.

Department of Chemistry, Yuvaraja's College, University of Mysore, Mysuru 570005, Karnataka, India.

出版信息

Biomedicines. 2023 Oct 6;11(10):2716. doi: 10.3390/biomedicines11102716.

Nuclear factor kappa B (NF-κB) is a potential therapeutic target in breast cancer. In the current study, a new class of oxazine- and piperazine-linked pyrimidines was developed as inhibitors of NF-κB, overcoming the complexity of the oxazine structure found in nature and enabling synthesis under laboratory conditions. Among the series of synthesized and tested oxazine-pyrimidine and piperazine-pyrimidine derivatives, compounds and inhibited breast cancer cell (MCF-7) viability with an IC value of 9.17 and 6.29 µM, respectively. docking studies showed that the pyrimidine ring of and the 4-methoxybenzyl thiol group of could strongly bind the p65 subunit of NF-κB, with the binding energies -9.32 and -7.32 kcal mol. Furthermore, compounds and inhibited NF-κB in MCF-7 breast cancer cells. In conclusion, we herein report newer structures that target NF-κB in BC cells.

核因子κB（NF-κB）是乳腺癌潜在的治疗靶点。在当前研究中，开发了一类新型的恶嗪和哌嗪连接的嘧啶作为NF-κB抑制剂，克服了自然界中发现的恶嗪结构的复杂性，并能够在实验室条件下进行合成。在一系列合成和测试的恶嗪-嘧啶和哌嗪-嘧啶衍生物中，化合物和分别以9.17和6.29 µM的IC值抑制乳腺癌细胞（MCF-7）的活力。对接研究表明，化合物的嘧啶环和化合物的4-甲氧基苄基硫醇基团可与NF-κB的p65亚基强烈结合，结合能分别为-9.32和-7.32 kcal/mol。此外，化合物和可抑制MCF-7乳腺癌细胞中的NF-κB。总之，我们在此报告了靶向乳腺癌细胞中NF-κB的新结构。