Department of Organic Chemistry and Biochemistry, Ruđer Bošković Institute, Zagreb, Croatia.
Division of Molecular Medicine, Ruđer Bošković Institute, Zagreb, Croatia.
Arch Pharm (Weinheim). 2020 Jun;353(6):e2000024. doi: 10.1002/ardp.202000024. Epub 2020 Apr 14.
In this study, three groups of adamantylphthalimides, bearing different substituents at the phthalimide moiety, N-(4'-R )phthalimidoadamantanes (1-7), 3-[N-(4'-R )phthalimido]-1-adamantanols (8-10), and 3-[N-(4'-R )phthalimido]adamantane-1-carboxylic acids (11-15), were synthesized and screened against tumor cells and viruses. The most potent compounds are not substituted at the adamantane and bear an OH or NH substituent at the phthalimide (compounds 3 and 5). The antiproliferative activities of compounds 3 and 5 are in the micromolar range, much higher than the one of thalidomide. A minor antiviral activity against cytomegalovirus and varicella-zoster virus was found for compounds 3 and 5, but these compounds lacked selectivity. The results presented are important for the rational design of the next-generation compounds with anticancer and antiviral activities.
在这项研究中，三组金刚烷酰基邻苯二甲酰亚胺，在邻苯二甲酰亚胺部分带有不同的取代基，N-(4'-R')邻苯二甲酰亚胺金刚烷（1-7），3-[N-(4'-R')邻苯二甲酰亚胺]-1-金刚烷醇（8-10）和 3-[N-(4'-R')邻苯二甲酰亚胺]金刚烷-1-羧酸（11-15）被合成并对肿瘤细胞和病毒进行了筛选。最有效的化合物在金刚烷上没有取代基，并且在邻苯二甲酰亚胺上带有 OH 或 NH 取代基（化合物 3 和 5）。化合物 3 和 5 的抗增殖活性在微摩尔范围内，远高于沙利度胺。化合物 3 和 5 对巨细胞病毒和水痘带状疱疹病毒有轻微的抗病毒活性，但这些化合物缺乏选择性。所呈现的结果对于具有抗癌和抗病毒活性的下一代化合物的合理设计非常重要。
