Kadela-Tomanek Monika, Bębenek Ewa, Chrobak Elwira, Latocha Małgorzata, Boryczka Stanisław
Department of Organic Chemistry, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 4 Jagiellońska Str., 41-200 Sosnowiec, Poland.
Department of Cell Biology, School of Pharmacy with the Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia in Katowice, 8 Jedności Str., 41-200 Sosnowiec, Poland.
Molecules. 2017 Mar 11;22(3):447. doi: 10.3390/molecules22030447.
The compounds produced by a living organism are most commonly as medicinal agents and starting materials for the preparation of new semi-synthetic derivatives. One of the largest groups of natural compounds consists of products containing a 1,4-benzoquinone subunit. This fragment occurs in three enediyne antibiotics, dynemicin A, deoxydynemicin A, and uncilamicin, which exhibit high biological activity. A series of alkoxy derivatives containing 1,4-naphthoquinone, 5,8-quinolinedione, and 2-methyl-5,8-quinolinedione moieties was synthesized. Moreover, the 1,4-benzoquinone subunit was contacted with an enediyne fragment. All obtained compounds were characterized by spectroscopy and spectrometry methods. The resulting alkane, alkene, alkyne and enediyne derivatives were tested as antitumor agents. They showed high cytotoxic activity depending on the type of 1,4-benzoquinone subunit and the employed tumor cell lines. The synthesized derivatives fulfill the Lipinski Rule of Five and have low permeability through the blood-brain barrier.
生物产生的化合物最常作为药物制剂和制备新的半合成衍生物的起始原料。最大的天然化合物组之一由含有1,4 - 苯醌亚基的产物组成。该片段存在于三种烯二炔抗生素中，即力达霉素A、脱氧力达霉素A和安丝菌素，它们具有很高的生物活性。合成了一系列含有1,4 - 萘醌、5,8 - 喹啉二酮和2 - 甲基 - 5,8 - 喹啉二酮部分的烷氧基衍生物。此外，使1,4 - 苯醌亚基与烯二炔片段接触。所有得到的化合物都通过光谱和光谱法进行了表征。所得的烷烃、烯烃、炔烃和烯二炔衍生物作为抗肿瘤剂进行了测试。它们根据1,4 - 苯醌亚基的类型和所使用的肿瘤细胞系表现出高细胞毒性活性。合成的衍生物符合Lipinski五规则，并且通过血脑屏障的渗透性较低。
