Indole Diterpenoids from an Endophytic Penicillium sp

  • J Nat Prod. 2019 Jun 28;82(6):1412-1423. doi: 10.1021/acs.jnatprod.8b00723.
Ni P Ariantari  1  2 ,  Elena Ancheeva  1 ,  Chenyin Wang  3 ,  Attila Mándi  4 ,  Tim-O Knedel  5 ,  Tibor Kurtán  4 ,  Chaidir Chaidir  6 ,  Werner E G Müller  7 ,  Matthias U Kassack  3 ,  Christoph Janiak  5 ,  Georgios Daletos  1 ,  Peter Proksch  1
Affiliations
  • 1. Institute of Pharmaceutical Biology and Biotechnology , Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany.
  • 2. Department of Pharmacy, Faculty of Mathematic and Natural Sciences , Udayana University , 80361 Bali , Indonesia.
  • 3. Institute of Pharmaceutical and Medicinal Chemistry , Heinrich Heine University Düsseldorf , Universitätsstrasse 1 , 40225 Düsseldorf , Germany.
  • 4. Department of Organic Chemistry , University of Debrecen , P.O.B. 400, 4002 Debrecen , Hungary.
  • 5. Institute of Inorganic Chemistry and Structural Chemistry , Heinrich Heine University Düsseldorf , Universitätsstraße 1 , 40225 Düsseldorf , Germany.
  • 6. Center for Pharmaceutical and Medical Technology , Agency for the Assessment and Application Technology , 10340 Jakarta , Indonesia.
  • 7. Institute of Physiological Chemistry , Universitätsmedizin der Johannes Gutenberg-Universität Mainz , Duesbergweg 6 , 55128 Mainz , Germany.
PMID: 31117519 DOI: 10.1021/acs.jnatprod.8b00723
Abstract

A chemical investigation of the endophyte Penicillium sp. (strain ZO-R1-1), isolated from roots of the medicinal plant Zingiber officinale, yielded nine new indole Diterpenoids (1-9), together with 13 known congeners (10-22). The structures of the new compounds were elucidated by 1D and 2D NMR analysis in combination with HRESIMS data. The absolute configuration of the new natural products 1, 3, and 7 was determined using the TDDFT-ECD approach and confirmed for 1 by single-crystal X-ray determination through anomalous dispersion. The isolated compounds were tested for cytotoxicity against L5178Y, A2780, J82, and HEK-293 cell lines. Compound 1 was the most active metabolite toward L5178Y cells, with an IC50 value of 3.6 μM, and an IC50 against A2780 cells of 8.7 μM. Interestingly, 1 features a new type of indole diterpenoid scaffold with a rare 6/5/6/6/6/6/5 heterocyclic system bearing an aromatic ring C, which is suggested to be important for the cytotoxic activity of this natural product against L5278Y and A2780 cells.

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