Departamento de Química Orgánica y Farmacéutica, University of Navarra, Irunlarrea 1, E-31008 Pamplona, Spain.
Departamento de Ciencias de la Salud, Universidad Pública de Navarra, Avda. Barañain s/n, E-31008 Pamplona, Spain.
Eur J Med Chem. 2014 Aug 18;83:674-84. doi: 10.1016/j.ejmech.2014.06.076. Epub 2014 Jul 1.
A series of new aliphatic, aromatic and heteroaromatic carbamate derivatives containing a methylseleno moiety were synthesized and evaluated in vitro for their cytotoxic activity against a panel of human cell lines including CCRF-CEM (lymphoblastic leukaemia), K-562 (lymphocytic leukaemia), HT-29 (colon carcinoma), HTB-54 (lung carcinoma), PC-3 (prostate carcinoma), MCF-7 (breast adenocarcinoma), 184B5 (non-malignant, mammary gland derived) and BEAS-2B (non-malignant, derived from bronchial epithelium). Most of the compounds are highly cytotoxic with GI50 values below 10 μM in every tested tumour cell line. Based on its cytotoxic parameters, selectivity index and ADME profile, the biological activity of compound 2, the propyl derivative, was further analysed in CCRF-CEM and HTB-54 cells. Results showed that this compound is able to induce apoptosis in a time- and dose-dependent manner. Involvement of caspases in cell death induction by 2 was detected. Besides, compound 2 was also able to induce cell cycle arrest at G0/G1 in CCRF-CEM cells and at G2/M in HTB-54 cells.
一系列含有甲基硒基团的新型脂肪族、芳香族和杂环氨基甲酸酯衍生物被合成，并在体外对其针对包括 CCRF-CEM（淋巴母细胞白血病）、K-562（淋巴细胞白血病）、HT-29（结肠癌细胞）、HTB-54（肺癌细胞）、PC-3（前列腺癌细胞）、MCF-7（乳腺癌腺癌）、184B5（非恶性，乳腺来源）和 BEAS-2B（非恶性，支气管上皮来源）在内的一系列人类细胞系的细胞毒性活性进行了评估。大多数化合物具有高度的细胞毒性，在每个测试的肿瘤细胞系中的 GI50 值均低于 10 μM。基于其细胞毒性参数、选择性指数和 ADME 特性，进一步在 CCRF-CEM 和 HTB-54 细胞中分析了丙基衍生物 2 的生物学活性。结果表明，该化合物能够以时间和剂量依赖的方式诱导细胞凋亡。检测到 2 诱导细胞死亡涉及半胱天冬酶。此外，化合物 2 还能够诱导 CCRF-CEM 细胞中的细胞周期停滞在 G0/G1 期和 HTB-54 细胞中的 G2/M 期。
