Department of Pharmaceutical Chemistry, Faculty of Pharmacy, National and Kapodistrian University of Athens, Panepistimioupoli-Zografou, 15771 Athens, Greece.
J Med Chem. 2012 Nov 26;55(22):10241-61. doi: 10.1021/jm3013008. Epub 2012 Nov 9.
The synthesis of the adamantane phenylalkylamines 2a-d, 3a-c, and 4a-e is described. These compounds exhibited significant antiproliferative activity, in vitro, against eight cancer cell lines tested. The σ(1), σ(2), and sodium channel binding affinities of compounds 2a, 3a, 4a, and 4c-e were investigated. The most interesting analogue, 4a, exhibited significant in vivo anticancer profile on pancreas, prostate, leukemia, and ovarian cancer cell line xenografts together with apoptosis and caspase-3 activation. Inhibition of the cancer cells cycle at the sub-G1 level was also obtained with 4a. Finally, encouraging results were observed with 4a in vivo on mice, suggesting putative antimetastatic and analgesic activities of this compound.
本文描述了金刚烷苯烷基胺 2a-d、3a-c 和 4a-e 的合成。这些化合物在体外对 8 种测试的癌细胞系表现出显著的抗增殖活性。还研究了化合物 2a、3a、4a 和 4c-e 的 σ(1)、σ(2)和钠通道结合亲和力。最有趣的类似物 4a 在胰腺、前列腺、白血病和卵巢癌细胞系异种移植的体内具有显著的抗癌特性，同时还能诱导细胞凋亡和 caspase-3 激活。4a 还能使癌细胞周期在 sub-G1 水平抑制。最后，4a 在体内对小鼠的实验也取得了令人鼓舞的结果，这表明该化合物具有潜在的抗转移和镇痛活性。
