2. Academic Validation
  3. Himalaquinones A-G, Angucyclinone-Derived Metabolites Produced by the Himalayan Isolate Streptomyces sp. PU-MM59

Himalaquinones A-G, Angucyclinone-Derived Metabolites Produced by the Himalayan Isolate Streptomyces sp. PU-MM59

  • J Nat Prod. 2021 Jul 23;84(7):1930-1940. doi: 10.1021/acs.jnatprod.1c00192.
Yongyong Zhang 1,  Mohsin T Cheema 2,  Larissa V Ponomareva,  Qing Ye 3,  Tao Liu 4,  Imran Sajid 2,  Jürgen Rohr,  Qing-Bai She 3,  S Randal Voss,  Jon S Thorson,  Khaled A Shaaban
Affiliations

Affiliations

  • 1 Department of Pharmacy, College of Life Sciences, China Jiliang University, Hangzhou 310018, People's Republic of China.
  • 2 Institute of Microbiology and Molecular Genetics (MMG), University of the Punjab, Lahore 54590, Pakistan.
  • 3 Markey Cancer Center, Department of Pharmacology and Nutritional Sciences, College of Medicine, University of Kentucky, Lexington, Kentucky 40536, United States.
  • 4 Department of Natural Products Chemistry, School of Pharmacy, China Medical University, Shenyang 110122, People's Republic of China.
PMID: 34170698 DOI: 10.1021/acs.jnatprod.1c00192
Abstract

Himalaquinones A-G, seven new anthraquinone-derived metabolites, were obtained from the Himalayan-based Streptomyces sp. PU-MM59. The chemical structures of the new compounds were identified based on cumulative analyses of HRESIMS and NMR spectra. Himalaquinones A-F were determined to be unique Anthraquinones that contained unusual C-4a 3-methylbut-3-enoic acid aromatic substitutions, while himalaquinone G was identified as a new 5,6-dihydrodiol-bearing angucyclinone. Comparative bioactivity assessment (antimicrobial, Cancer cell line cytotoxicity, impact on 4E-BP1 phosphorylation, and effect on axolotl embryo tail regeneration) revealed cytotoxic landomycin and saquayamycin analogues to inhibit 4E-BP1p and inhibit regeneration. In contrast, himalaquinone G, while also cytotoxic and a regeneration inhibitor, did not affect 4E-BP1p status at the doses tested. As such, this work implicates a unique mechanism for himalaquinone G and possibly Other 5,6-dihydrodiol-bearing angucyclinones.

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