New Bioactive β-Resorcylic Acid Derivatives from the Alga-Derived Fungus Penicillium antarcticum KMM 4685

  • Mar Drugs. 2023 Mar 14;21(3):178. doi: 10.3390/md21030178.
Elena V Leshchenko  1  2 ,  Alexandr S Antonov  1 ,  Gleb V Borkunov  1  2 ,  Jessica Hauschild  3  4 ,  Olesya I Zhuravleva  1  2 ,  Yuliya V Khudyakova  1 ,  Alexander S Menshov  1 ,  Roman S Popov  1 ,  Natalya Yu Kim  1 ,  Markus Graefen  4 ,  Carsten Bokemeyer  3 ,  Gunhild von Amsberg  3  4 ,  Anton N Yurchenko  1 ,  Sergey A Dyshlovoy  3  4
Affiliations
  • 1. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, 159 Prospect 100-letiya Vladivostoka, Vladivostok 690022, Russia.
  • 2. Institute of High Technologies and Advanced Materials, Far Eastern Federal University, Vladivostok 690922, Russia.
  • 3. Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald Tumorzentrum-University Cancer Center Hamburg (UCCH), University Medical Center Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
  • 4. Martini-Klinik, Prostate Cancer Center, University Hospital Hamburg-Eppendorf, Martinistrasse 52, 20246 Hamburg, Germany.
PMID: 36976227 DOI: 10.3390/md21030178
Abstract

Five new β-resorcylic acid derivatives, 14-hydroxyasperentin B (1), β-resoantarctines A-C (3, 5, 6) and 8-dehydro-β-resoantarctine A (4), together with known 14-hydroxyasperentin (5'-hydroxyasperentin) (2), were isolated from the ethyl acetate extract of the fungus Penicillium antarcticum KMM 4685 associated with the brown alga Sargassum miyabei. The structures of the compounds were elucidated by spectroscopic analyses and modified Mosher's method, and the biogenetic pathways for compounds 3-6 were proposed. For the very first time, the relative configuration of the C-14 center of a known compound 2 was assigned via analyses of magnitudes of the vicinal coupling constants. The new metabolites 3-6 were biogenically related to resorcylic acid lactones (RALs); however, they did not possess lactonized Macrolide elements in their structures. Compounds 3, 4 and 5 exhibited moderate cytotoxic activity in LNCaP, DU145 and 22Rv1 human prostate Cancer cells. Moreover, these metabolites could inhibit the activity of P-glycoprotein at their noncytotoxic concentrations and consequently synergize with docetaxel in p-glycoprotein-overexpressing drug-resistant Cancer cells.

Keywords
Penicillium antarcticum; marine-derived fungus; p-glycoprotein inhibitory activity; prostate cancer; secondary metabolites; β-resorcylic acid.
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