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Ansamycin derivatives from the marine-derived Streptomyces sp. SCSGAA 0027 and their cytotoxic and antiviral activities.
Bioorganic & Medicinal Chemistry Letters ( IF 2.7 ) Pub Date : 2020-04-03 , DOI: 10.1016/j.bmcl.2020.127168
Xu-Hua Nong 1 , Zheng-Chao Tu 2 , Shu-Hua Qi 1
Affiliation  

Fourteen ansamycin derivatives including seven new herbimycins G-L (1-6) and divergolide O (7), and seven known analogues were isolated from a culture broth of the marine-derived Streptomyces sp. SCSGAA 0027. Their complete structures were determined by detailed analysis of spectroscopic data and quantum chemical calculations. Compounds 1-5 and 7 featured an additional eight-membered O-heterocycle that has rarely been reported for ansamycins, and the Z,Z- and E,E-configurations for Δ2,Δ4 were reported for the first time in geldanamycin analogues. Compound 1 exhibited weak inhibition activity towards Hsp90α with an IC50 value of 96 µM, 2-5 showed mild cytotoxicity against four human cancer cell lines with IC50 values ranging from 13 μM to 86 μM, and 7 had moderate anti-HSV-1 activity with an IC50 value of 19 µM and very weak cytotoxicity towards Vero cell. The possible biosynthetic pathways for 1-5 were proposed. And their structure-bioactivity relationship was also discussed.

中文翻译:

来自海洋的链霉菌sp。的安沙霉素衍生物。SCSGAA 0027及其细胞毒性和抗病毒活性。

从海洋来源的链霉菌属菌种的培养液中分离了十四种安沙霉素衍生物,包括七种新的除草霉素GL(1-6)和曲格列奈O(7),以及七种已知类似物。SCSGAA0027。它们的完整结构是通过对光谱数据的详细分析和量子化学计算确定的。化合物1-5和7的特征是另外一个八元的O杂环,这很少报道过安沙霉素,而在格尔德霉素类似物中首次报道了Δ2,Δ4的Z,Z和E,E构型。化合物1对Hsp90α的抑制活性较弱,IC50值为96 µM,化合物2-5对4种人类癌细胞系的IC50值为13μM至86μM的细胞毒性较弱,7和7具有中等的抗HSV-1活性,IC50值为19 µM,并且对Vero细胞的细胞毒性非常弱。提出了1-5的可能的生物合成途径。并讨论了它们的结构生物活性关系。
更新日期:2020-04-20
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