吉西他滨的噻吩扩展鸟苷类似物。
Thiophene-expanded guanosine analogues of Gemcitabine.
作者信息
Chen Zhe, Ku Therese C, Seley-Radtke Katherine L
机构信息
University of Maryland, Baltimore County, Department of Chemistry & Biochemistry, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
University of Maryland, Baltimore County, Department of Chemistry & Biochemistry, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
出版信息
Bioorg Med Chem Lett. 2015 Oct 1;25(19):4274-6. doi: 10.1016/j.bmcl.2015.07.086. Epub 2015 Jul 30.
Abstract
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).
摘要
化疗药物吉西他滨，即2',2'-二氟-2'-脱氧胞苷，长期以来一直是多种癌症的治疗标准。吉西他滨的化疗特性源于其2',2'-二氟-2'-脱氧核糖糖，它模仿天然核苷，但也会破坏核酸合成，导致细胞死亡。因此，人们制备了许多类似物，以进一步探索这种结构修饰的生物学意义。在这方面，一种噻吩扩展的鸟苷类似物因其先前观察到的三环杂碱基支架的生物活性而受到关注。制备了几种类似物，包括麦圭根前药，但母体核苷表现出最佳的化疗活性，特别是对乳腺癌细胞系（生长抑制率89.53%）。
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