Department of Chemistry, Jinan University, Guangzhou, 510632, China.
ChemMedChem. 2018 Oct 22;13(20):2202-2207. doi: 10.1002/cmdc.201800529. Epub 2018 Sep 5.
The total synthesis of reniochalistatins A-E, along with a reniochalistatin E analogue (inverso-E) was successfully achieved through Fmoc-based solid-phase peptide synthesis and subsequent macrolactamization with PyBOP and DIEA. The biological activities of these reniochalistatins and a key linear peptide intermediate were systematically evaluated. Among these seven synthesized compounds, linear reniochalistatin B was found to have potent activity against several cancer cell lines not shown by the cyclic reniochalistatin B counterpart. In addition, linear reniochalistatin B was found to have antitubercular activity (IC =1.4 μm). Inverso-E possesses increasing cytotoxicity against the HeLa and LNCaP cell lines after simple alternation of the sequence of amino acids in reniochalistatin E. The results of these studies provide a feasible method to further investigate the structure-activity relationships (SARs) of reniochalistatins A-E.
通过基于 Fmoc 的固相肽合成以及随后使用 PyBOP 和 DIEA 进行大环内酯化，成功地实现了雷尼奥沙利他汀 A-E 的全合成，以及雷尼奥沙利他汀 E 的类似物（逆-E）。对这些雷尼奥沙利他汀和关键的线性肽中间产物进行了系统的生物活性评估。在这七种合成化合物中，线性雷尼奥沙利他汀 B 被发现对几种癌细胞系具有很强的活性，而环状雷尼奥沙利他汀 B 则没有表现出这种活性。此外，线性雷尼奥沙利他汀 B 还具有抗结核活性（IC =1.4 μm）。逆-E 只是简单地改变了雷尼奥沙利他汀 E 中氨基酸的序列，对 HeLa 和 LNCaP 细胞系的细胞毒性就有所增加。这些研究的结果为进一步研究雷尼奥沙利他汀 A-E 的构效关系（SAR）提供了一种可行的方法。
