Asperindoles A⁻D and a p-Terphenyl Derivative from the Ascidian-Derived Fungus Aspergillus sp. KMM 4676

  • Mar Drugs. 2018 Jul 9;16(7):232. doi: 10.3390/md16070232.
Elena V Ivanets  1 ,  Anton N Yurchenko  2 ,  Olga F Smetanina  3 ,  Anton B Rasin  4 ,  Olesya I Zhuravleva  5  6 ,  Mikhail V Pivkin  7 ,  Roman S Popov  8 ,  Gunhild von Amsberg  9 ,  Shamil Sh Afiyatullov  10 ,  Sergey A Dyshlovoy  11  12  13
Affiliations
  • 1. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 2. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 3. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 4. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 5. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 6. School of Natural Science, Far Eastern Federal University, Sukhanova St., 8, Vladivostok 690000, Russia. [email protected].
  • 7. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 8. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 9. Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. [email protected].
  • 10. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 11. G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far Eastern Branch of the Russian Academy of Sciences, Prospect 100-letiya Vladivostoka, 159, Vladivostok 690022, Russia. [email protected].
  • 12. School of Natural Science, Far Eastern Federal University, Sukhanova St., 8, Vladivostok 690000, Russia. [email protected].
  • 13. Laboratory of Experimental Oncology, Department of Oncology, Hematology and Bone Marrow Transplantation with Section Pneumology, Hubertus Wald-Tumorzentrum, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany. [email protected].
PMID: 29987238 DOI: 10.3390/md16070232
Abstract

Four new indole-diterpene Alkaloids asperindoles A⁻D (1⁻4) and the known p-terphenyl derivative 3″-hydroxyterphenyllin (5) were isolated from the marine-derived strain of the fungus Aspergillus sp., associated with an unidentified colonial ascidian. The structures of 1⁻5 were established by 2D NMR and HRESIMS data. The absolute configurations of all stereocenters of 1⁻4 were determined by the combination of ROESY data, coupling constants analysis, and biogenetic considerations. Asperindoles C and D contain a 2-hydroxyisobutyric acid (2-HIBA) residue, rarely found in natural compounds. Asperindole A exhibits cytotoxic activity against hormone therapy-resistant PC-3 and 22Rv1, as well as hormone therapy-sensitive human prostate Cancer cells, and induces Apoptosis in these cells at low-micromolar concentrations.

Keywords
cytotoxicity; indole-diterpenoids; marine-derived fungi; secondary metabolites.
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