Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Bijenička 54, 10000 Zagreb, Croatia.
Chem Biol Drug Des. 2012 Apr;79(4):497-506. doi: 10.1111/j.1747-0285.2011.01305.x. Epub 2012 Jan 30.
A series of (1-adamantyl)phthalimides, 1-4, and (2-adamantyl)phthalimides, 5-8, characterized by different chain length between the adamantyl and the phthalimide moiety were synthesized, as well as 1- and 2-adamantylphthalimides substituted by nitro 9, 10, and amino group 11, 12, and phthalimides bearing homoadamantyl 13 and protoadamantyl substituent 14 and 15. The compounds were tested for antiproliferative activity in vitro on a series of five human cancer lines: MCF-7 (breast carcinoma), SW 620 (colon carcinoma), HCT 116 (colon carcinoma), MOLT-4 (acute lymphoblastic leukemia), H 460 (lung carcinoma), and a non-tumor cell line HaCaT (human keratinocytes). All compounds except nitro derivatives 9 and 10 exhibited antiproliferative activity. The activity was generally better in the 2-adamantyl series 5-8 and in the compounds having the longest alkyl spacers as in 4 and 8, or with an amino group as in 9 and 10. The most active compounds with the propylene spacer 4 and 8 showed the highest selectivity toward tumor cells. The activity was found to be due to a delay in the progress through the cell cycle at G1/S phase.
一系列（1-金刚烷基）邻苯二甲酰亚胺，1-4 和（2-金刚烷基）邻苯二甲酰亚胺，5-8，其特征在于金刚烷基和邻苯二甲酰亚胺部分之间的链长不同，以及 1-和 2-金刚烷基邻苯二甲酰亚胺被硝基取代 9、10 和氨基取代 11、12，以及带有同金刚烷基取代基 13 和原金刚烷基取代基 14 和 15 的邻苯二甲酰亚胺。这些化合物在体外对一系列五种人类癌细胞系进行了抗增殖活性测试：MCF-7（乳腺癌）、SW 620（结肠癌）、HCT 116（结肠癌）、MOLT-4（急性淋巴细胞白血病）、H 460（肺癌）和非肿瘤细胞系 HaCaT（人角质形成细胞）。除了硝基衍生物 9 和 10 之外，所有化合物都表现出抗增殖活性。2-金刚烷基系列 5-8 中的活性通常更好，在具有最长烷基间隔基的化合物中，如 4 和 8，或具有氨基的化合物中，如 9 和 10，活性更好。具有丙烯间隔基 4 和 8 的最活性化合物对肿瘤细胞表现出最高的选择性。该活性被发现是由于细胞周期在 G1/S 期的进展延迟。
