Thiophene-expanded guanosine analogues of Gemcitabine

详细信息    查看全文

• 作者：Zhe Chen ; Therese C. Ku ; Katherine L. Seley-Radtke ; ^{kseley@umbc.edu" class="auth_mail" title="E-mail the corresponding author}
• 关键词：Tricyclic ; Nucleosides ; Expanded guanosine ; 2&prime ; 2&prime ; -Difluoro-2&prime ; -deoxycytidine ; Cancer
• 刊名：Bioorganic & Medicinal Chemistry Letters
• 出版年：2015
• 出版时间：1 October 2015
• 年：2015
• 卷：25
• 期：19
• 页码：4274-4276
• 全文大小：545 K

文摘

The chemotherapeutic drug Gemcitabine, 2′,2′-difluoro-2′-deoxycytidine, has long been the standard of care for a number of cancers. Gemcitabine’s chemotherapeutic properties stem from its 2′,2′-difluoro-2′-deoxyribose sugar, which mimics the natural nucleoside, but also disrupts nucleic acid synthesis, leading to cell death. As a result, numerous analogues have been prepared to further explore the biological implications for this structural modification. In that regard, a thieno-expanded guanosine analogue was of interest due to biological activity previously observed for the tricyclic heterobase scaffold. Several analogues were prepared, including the McGuigan ProTide, however the parent nucleoside exhibited the best chemotherapeutic activity, specifically against breast cancer cell lines (89.53% growth inhibition).