Synthesis and Biological Evaluation of Reniochalistatins A–E and a Reniochalistatin E Analogue,ChemMedChem

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Synthesis and Biological Evaluation of Reniochalistatins A–E and a Reniochalistatin E Analogue
ChemMedChem ( IF 3.6 ) Pub Date : 2018-09-05 , DOI: 10.1002/cmdc.201800529
Rong Zhou ₁ , Yueguang Sun ₁ , Hangbin Li ₁ , Weili Long ₁ , Xiaojian Liao ₁ , Pengju Feng ₁ , Shihai Xu ₁

Affiliation

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 (IC₅₀=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.

中文翻译：

肾上腺壳抑素A–E和肾上腺壳抑素E类似物的合成及生物学评价

通过基于Fmoc的固相肽合成以及随后用PyBOP和DIEA进行大内酰胺化，成功地完成了肾chalistalatins A–E的全合成以及renchachalistatin E类似物（inverso-E）。系统地评估了这些肾上腺抑素和关键线性肽中间体的生物活性。在这七个合成的化合物中，发现线性肾上腺抑素B具有对几种癌细胞的有效活性，而环状肾上腺抑素B对应物未显示这些癌细胞系。此外，线性reniochalistatin乙被发现具有抗结核活性（IC ₅₀ = 1.4μ米）。简单改变肾上腺抑素E中的氨基酸序列后，Inverso-E对HeLa和LNCaP细胞系的细胞毒性增加。这些研究结果为进一步研究肾上腺抑素A-的结构-活性关系（SAR）提供了一种可行的方法。 E．

更新日期：2018-09-05

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