Anti-diabetic and anti-inflammatory indole diterpenes from the marine-derived fungus Penicillium sp. ZYX-Z-143

  • Bioorg Chem. 2024 Apr:145:107205. doi: 10.1016/j.bioorg.2024.107205.
Lu-Ting Dai  1 ,  Li Yang  2 ,  Jiao-Cen Guo  2 ,  Qing-Yun Ma  2 ,  Qing-Yi Xie  2 ,  Li Jiang  3 ,  Zhi-Fang Yu  4 ,  Hao-Fu Dai  5 ,  You-Xing Zhao  6
Affiliations
  • 1. Key Laboratory of Research and Development of Natural Product from Li Folk Medicine of Hainan Province & National Key Laboratory for Tropical Crop Breeding, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China; College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
  • 2. Key Laboratory of Research and Development of Natural Product from Li Folk Medicine of Hainan Province & National Key Laboratory for Tropical Crop Breeding, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China.
  • 3. College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China.
  • 4. College of Food Science and Technology, Nanjing Agricultural University, Nanjing 210095, China. Electronic address: [email protected].
  • 5. Key Laboratory of Research and Development of Natural Product from Li Folk Medicine of Hainan Province & National Key Laboratory for Tropical Crop Breeding, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China. Electronic address: [email protected].
  • 6. Key Laboratory of Research and Development of Natural Product from Li Folk Medicine of Hainan Province & National Key Laboratory for Tropical Crop Breeding, Institute of Tropical Bioscience and Biotechnology, Chinese Academy of Tropical Agricultural Sciences, Haikou 571101, China. Electronic address: [email protected].
PMID: 38387395 DOI: 10.1016/j.bioorg.2024.107205
Abstract

Seven new indole-diterpenoids, penpaxilloids A-E (1-5), 7-methoxypaxilline-13-ene (6), and 10-hydroxy-paspaline (7), along with 20 known ones (8-27), were isolated from the marine-derived fungus Penicillium sp. ZYX-Z-143. Among them, compound 1 was a spiro indole-diterpenoid bearing a 2,3,3a,5-tetrahydro-1H-benzo[d]pyrrolo[2,1-b][1,3]oxazin-1-one motif. Compound 2 was characterized by a unique heptacyclic system featuring a rare 3,6,8-trioxabicyclo[3.2.1]octane unit. The structures of the new compounds were established by extensive spectroscopic analyses, NMR calculations coupled with the DP4 + analysis, and ECD calculations. The plausible biogenetic pathway of two unprecedented indole Diterpenoids, penpaxilloids A and B (1 and 2), was postulated. Compound 1 acted as a noncompetitive inhibitor against protein tyrosine Phosphatase 1B (PTP1B) with IC50 value of 8.60 ± 0.53 μM. Compound 17 showed significant α-glucosidase inhibitory activity with IC50 value of 19.96 ± 0.32 μM. Moreover, compounds 4, 8, and 22 potently suppressed nitric oxide production on lipopolysaccharide-stimulated RAW264.7 macrophages.

Keywords
Anti-inflammatory; Indole diterpenoids; PTP1B; Penicillium sp.; α-glucosidase.
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