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Design, synthesis and biological evaluation of new carbazole derivatives as anti-cancer and anti-migratory agents
Bioorganic & Medicinal Chemistry ( IF 3.5 ) Pub Date : 2018-01-11 , DOI: 10.1016/j.bmc.2018.01.003
Cornelis P Vlaar 1 , Linette Castillo-Pichardo 2 , Julia I Medina 1 , Cathyria M Marrero-Serra 1 , Ericka Vélez 1 , Zulma Ramos 1 , Eliud Hernández 1
Affiliation  

Based on the efficacy of EHop-016 as an inhibitor of migration and Rac1 activation, a new series of carbazole derivatives has been synthesized. Cytotoxic and anti-migratory effects of these compounds were evaluated in MCF-7 and MDA-MB-231 breast cancer cell lines. Preliminary investigations of their anticancer activity demonstrated that several compounds have moderate antiproliferative effects on cancer cell lines with GI50 values in the range of 13–50 µM. Furthermore, compounds 3b and 11b inhibit migration activity of metastatic cell line MDA-MB-231 by 32% and 34%, respectively. Compound 11b was shown to inhibit activation of the Rho GTPase Rac1 by 55% at 250 nM in both MDA-MB-231 and MDA-MB-435 cell lines. Compared with the IC50 of Rac1 inhibition by lead compound EHop-016 of 1.1 µM, compound 11b demonstrates 4X improved in vitro efficacy.



中文翻译:

新型咔唑衍生物作为抗癌和抗迁移剂的设计、合成和生物学评价

基于EHop-016作为迁移和Rac1激活抑制剂的功效,合成了一系列新的咔唑衍生物。在 MCF-7 和 MDA-MB-231 乳腺癌细胞系中评估了这些化合物的细胞毒性和抗迁移作用。对其抗癌活性的初步研究表明,几种化合物对 GI 50值在 13–50 µM 范围内的癌细胞系具有中等抗增殖作用。此外,化合物3b11b分别抑制转移细胞系MDA-MB-231的迁移活性32%和34%。在 MDA-MB-231 和 MDA-MB-435 细胞系中,化合物11b在 250 nM 时可抑制 Rho GTPase Rac1 的激活 55%。与先导化合物 EHop-016 的 1.1 µM Rac1 抑制作用的IC 50相比,化合物11b 的体外功效提高了 4 倍。

更新日期:2018-01-11
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