Alcolea Verónica, Plano Daniel, Karelia Deepkamal N, Palop Juan Antonio, Amin Shantu, Sanmartín Carmen, Sharma Arun K
Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA; Department of Organic and Pharmaceutical Chemistry, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain; Instituto de Investigación Sanitaria de Navarra (IdiSNA), Irunlarrea 3, E-31008 Pamplona, Spain.
Department of Pharmacology, Penn State Hershey Cancer Institute, CH72, Penn State College of Medicine, 500 University Drive, Hershey, PA 17033, USA.
Eur J Med Chem. 2016 May 4;113:134-44. doi: 10.1016/j.ejmech.2016.02.042. Epub 2016 Feb 18.
A series of novel selenourea derivatives and corresponding thiourea analogs were synthesized and tested against a panel of six human cancer cell lines: melanoma (1205Lu), lung carcinoma (A549), prostatic carcinoma (DU145), colorectal carcinoma (HCT116), pancreatic epithelioid carcinoma (PANC-1) and pancreatic adenocarcinoma (BxPC3). In general, we found that the selenium-containing derivatives were more potent than their isosteric sulfur analogs. Four selenourea derivatives (1e, 1f, 1g and 1i) showed IC50 values below 10 μM in all of tested cell lines at 72 h. On the basis of its potent activity, compound 1g was selected for further biological evaluation in different colon cancer cell lines. Our results indicated that compound 1g induced apoptosis by caspase activation, along with inhibition of anti-apoptotic proteins.
合成了一系列新型硒脲衍生物及其相应的硫脲类似物，并针对六种人类癌细胞系进行了测试：黑色素瘤（1205Lu）、肺癌（A549）、前列腺癌（DU145）、结肠直肠癌（HCT116）、胰腺上皮样癌（PANC-1）和胰腺腺癌（BxPC3）。总体而言，我们发现含硒衍生物比其等电子硫类似物更具活性。四种硒脲衍生物（1e、1f、1g和1i）在72小时时在所有测试细胞系中的IC50值均低于10μM。基于其强大的活性，选择化合物1g在不同结肠癌细胞系中进行进一步的生物学评估。我们的结果表明，化合物1g通过激活半胱天冬酶诱导细胞凋亡，同时抑制抗凋亡蛋白。
