Departamento de Química Orgânica, Programa de Pós-Graduação em Química, Universidade Federal Fluminense, Outeiro de São João Batista, 24020-141, Niterói, RJ, Brazil.
Departamento de Fármacos e Medicamentos, Faculdade de Farmácia, Universidade Federal do Rio de Janeiro, Av. Carlos Chagas Filho, 373, CCS, Bss 31, 21941-599, Rio de Janeiro, RJ, Brazil.
Future Med Chem. 2018 Mar 1;10(5):527-540. doi: 10.4155/fmc-2017-0173. Epub 2018 Feb 9.
Cancer has emerged as a growing public health problem in many parts of the world.
We describe the synthesis of a series of carbohydrate-based isoquinoline-5,8-diones through the 1,4-addition reaction between 5,8-dioxo-5,8-dihydroisoquinoline and aminocarbohydrates. Halogenated quinones were also synthesized. Their inhibitory effects on the proliferation of human cancer cell lines were studied.
RESULTS & CONCLUSION: The most promising compound, derived from isoquinoline-5,8-dione, containing ribofuranosidyl ring, was selectively active in vitro against H1299 cancer cells, with 1.7-fold higher activity than that of vinorelbine tartrate. This result suggests that the glycoconjugate in question may constitute a valuable lead compound to design and synthesize a more active and less toxic derivative with respect to the development of a new antitumor substance.
癌症已成为世界许多地区日益严重的公共卫生问题。
我们通过 5,8-二氧代-5,8-二氢异喹啉与氨基糖的 1,4-加成反应，描述了一系列基于碳水化合物的异喹啉-5,8-二酮的合成。还合成了卤代醌。研究了它们对人癌细胞系增殖的抑制作用。
最有前途的化合物，来源于异喹啉-5,8-二酮，含有呋喃核糖基环，对 H1299 癌细胞具有体外选择性活性，其活性比酒石酸长春瑞滨高 1.7 倍。该结果表明，所研究的糖缀合物可能构成有价值的先导化合物，可用于设计和合成更有效和毒性更低的衍生物，以开发新的抗肿瘤物质。
