Synthesis of Antimitotic Thioglycosides: In Vitro and in Vivo Evaluation of Their Anticancer Activity
详细信息 查看全文
- 作者：Isabel Garc铆a-脕lvarez ; Hugo Groult ; Josefina Casas ; M. Asunci贸n Barreda-Manso ; Natalia Yanguas-Cas谩s ; Manuel Nieto-Sampedro ; Lorenzo Romero-Ram铆rez ; Alfonso Fern谩ndez-Mayoralas
- 刊名：Journal of Medicinal Chemistry
- 出版年：2011
- 出版时间：October 13, 2011
- 年：2011
- 卷：54
- 期：19
- 页码：6949-6955
- 全文大小：846K
- 年卷期：v.54,no.19(October 13, 2011)
- ISSN：1520-4804
文摘
The synthesis and biological activity of oleylN-acetyl-伪- and 尾-d-glucosaminides (1 and 2, respectively) and their thioglycosyl analogues (3 and 4, respectively) are reported. The compounds exhibited antimitotic activity on rat glioma (C6) and human lung carcinoma (A549) cell cultures in the micromolar range. Analysis of cell extracts using ultra performance liquid chromatography鈥搈ass spectrometry showed that the synthetic glycosides produce alterations in glycosphingolipid metabolism, with variable effect on the level of glucosylceramide depending on the configuration of the antimitotic used. In vivo experiments in nude mice bearing an implanted C6 glioma showed that the 伪-thioglycoside 3 reduced tumor volume, while the O-glycosyl derivative was inactive, highlighting the importance of using enzyme resistant glycosides.