2. Academic Validation
  3. Ansamycin derivatives from the marine-derived Streptomyces sp. SCSGAA 0027 and their cytotoxic and antiviral activities

Ansamycin derivatives from the marine-derived Streptomyces sp. SCSGAA 0027 and their cytotoxic and antiviral activities

  • Bioorg Med Chem Lett. 2020 Jun 1;30(11):127168. doi: 10.1016/j.bmcl.2020.127168.
Xu-Hua Nong 1,  Zheng-Chao Tu 2,  Shu-Hua Qi 3
Affiliations

Affiliations

  • 1 Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong, Key Laboratory of Marine Materia Medica/RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301 Guangdong, China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), 1119 Haibin Road, Nansha District, Guangzhou 511458, China.
  • 2 Guangzhou Institutes of Biomedicine and Health, Chinese Academy of Sciences, 190 Kaiyuan Road, Guangzhou 510530, China.
  • 3 Key Laboratory of Tropical Marine Bio-resources and Ecology/Guangdong, Key Laboratory of Marine Materia Medica/RNAM Center for Marine Microbiology, South China Sea Institute of Oceanology, Chinese Academy of Sciences, 164 West Xingang Road, Guangzhou 510301 Guangdong, China; Southern Marine Science and Engineering Guangdong Laboratory (Guangzhou), 1119 Haibin Road, Nansha District, Guangzhou 511458, China. Electronic address: [email protected].
PMID: 32273216 DOI: 10.1016/j.bmcl.2020.127168
Abstract

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.

Keywords

Ansamycin; Cytotoxicity; Divergolide; Herbimycin; Hsp90 inhibition; Streptomyces sp.; anti-HSV-1 activity.

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