Exploring the physicochemical and antiproliferative properties of biaryl-linked [13]-macrodilactones
Exploring the physicochemical and antiproliferative properties of biaryl-linked [13]-macrodilactones
复制标题
探索联芳基连接的[13]-大分子双内酯的理化和抗增殖特性
DOI：
10.1016/j.bmc.2020.115671
复制
发表时间：
2020
影响因子：
3.5
通讯作者：
Peczuh, Mark W.
中科院分区：
文献类型：
--
作者：
Chen, Chengsheng;Bosko, Cristin;McGeough, Catherine;McLean, Ryan;Zaino, Angela M.;Kyle Hadden, M.;Peczuh, Mark W.
一个大环基序促进了富有成效的蛋白质-小分子相互作用。有许多天然产物和人工合成的大循环的例子，这些大循环调节免疫系统，减缓微生物感染，或杀死真核细胞。本文报道了一组带有侧链联芳基的[13]-大双内酯的合成、理化表征和抗增殖活性。联芳基类似物是通过Suzuki反应在一个普通中间体上进行的，该中间体包含一个溴苯基单位α到[13]-大二内酯的一个羰基。主成分分析将新化合物放在相对于各种药物和天然产品的物理化学环境中。在小鼠基底细胞癌细胞系ASZ细胞中观察到适度的增殖抑制。这项工作强调了一种鉴定生物活性化合物的方法的价值，这种方法将物理化学参数的评估置于搜索过程的早期。
A macrocyclic motif fosters productive protein-small molecule interactions. There are numerous examples of both natural product and designed, synthetic macrocycles that modulate the immune system, slow microbial infection, or kill eukaryotic cells. Reported here are the synthesis, physicochemical characterization, and antiproliferative activity of a group of [13]-macrodilactones decorated with a pendant biaryl moiety. Biaryl analogs were prepared by Suzuki reactions conducted on a common intermediate that contained a bromophenyl unit alpha to one of the carbonyls of the [13]-macrodilactone. Principal component analysis placed the new compounds in physicochemical context relative to a variety of pharmaceuticals and natural products. Modest inhibition of proliferation was observed in ASZ cells, a murine basal cell carcinoma line. This work underscores the value of an approach toward the identification of bioactive compounds that places the evaluation of physicochemical parameters early in the search process.