Department of Chemistry and Biochemistry, South Dakota State University , Brookings, SD , USA.
J Enzyme Inhib Med Chem. 2014 Apr;29(2):162-7. doi: 10.3109/14756366.2012.762646. Epub 2013 Jan 31.
Cucurbitacins (Cucs) have been classified as signal transducer and activator of transcription 3 inhibitors. Kinase inhibition has been a validated drug target in multiple types of malignancies. B-RAF mutations are highly expressed in the melanoma. Our hypothesis is the Cucs can be a potential candidate to inhibit the signaling kinase pathway. The research presented is the evaluation of Cucs, as B-RAF and MEK1 kinase inhibitors. Virtual screening methods were employed to identify lead compounds. The hypothesis was tested on mutant B-RAF cell lines, A-375 and Sk-Mel-28 cell lines to determine the activity toward melanoma. A series of natural Cucs show an improved activity toward Sk-Mel-28 and A-375 cell lines. Cucs show potential inhibition for the total and phosphorylated ERK using ELISA kits. Cucs could be potential candidate for inhibiting cell growth.
葫芦素 (Cucs) 已被归类为信号转导和转录激活因子 3 抑制剂。激酶抑制已成为多种类型恶性肿瘤的有效药物靶点。黑色素瘤中高度表达 B-RAF 突变。我们的假设是，葫芦素可以成为抑制信号激酶通路的潜在候选物。本研究旨在评估葫芦素作为 B-RAF 和 MEK1 激酶抑制剂的作用。采用虚拟筛选方法来鉴定先导化合物。该假说在突变 B-RAF 细胞系 A-375 和 Sk-Mel-28 细胞系上进行了测试，以确定对黑色素瘤的活性。一系列天然葫芦素对 Sk-Mel-28 和 A-375 细胞系表现出改善的活性。ELISA 试剂盒显示葫芦素对总 ERK 和磷酸化 ERK 具有潜在的抑制作用。葫芦素可能是抑制细胞生长的潜在候选物。
