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

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

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. ev.ivanets@yandex.ru.
  • 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. yurchant@ya.ru.
  • 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. smetof@rambler.ru.
  • 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. abrus__54@mail.ru.
  • 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. zhuravleva.oi@dvfu.ru.
  • 6 School of Natural Science, Far Eastern Federal University, Sukhanova St., 8, Vladivostok 690000, Russia. zhuravleva.oi@dvfu.ru.
  • 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. oid27@mail.ru.
  • 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. prs_90@mail.ru.
  • 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. g.von-amsberg@uke.de.
  • 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. afiyat@piboc.dvo.ru.
  • 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. dyshlovoy@gmail.com.
  • 12 School of Natural Science, Far Eastern Federal University, Sukhanova St., 8, Vladivostok 690000, Russia. dyshlovoy@gmail.com.
  • 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. dyshlovoy@gmail.com.
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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