Antidiabetic xanthones with α-glucosidase inhibitory activities from an endophytic Penicillium canescens

Abd Malik, Hamidreza Ardalani, Syariful Anam, Laura Mikél McNair, Kresten J. K. Kromphardt, Rasmus John Normand Frandsen, Henrik Franzyk, Dan Staerk, Kenneth T. Kongstad

Research output: Contribution to journalArticlepeer-review

Abstract

Worldwide, 463 million people are affected by diabetes of which the majority is diagnosed with Type 2 Diabetes (T2D). T2D can ultimately lead to retinopathy, nephropathy, nerve damage, and amputation of the lower extremities. α-Glucosidase, responsible for converting starch to monosaccharides, is a key therapeutic target for the management of T2D. However, due to substantial side effects of currently marketed drugs, there is an urgent need for the discovery of new α-glucosidase inhibitors. In our ongoing efforts to identify novel α-glucosidase inhibitors from Nature, we are investigating the potential of endophytic filamentous fungi as sustainable sources of hits and/or leads for future antihyperglycemic drugs. Here we report one previously unreported xanthone (5) and two known xanthones (7 and 11) as α-glucosidase inhibitors, isolated from an endophytic Penicillium canescens, recovered from fruits of Juniperus polycarpos. The three xanthones 5, 7, and 11 showed inhibitory activities against α-glucosidase with IC50 values of 38.80 ± 1.01 μM, 32.32 ± 1.01 μM, and 75.20 ± 1.02 μM, respectively. Further pharmacological characterization revealed a mixed-mode inhibition for 5, a competitive inhibition for 7, while 11 acted as a non-competitive inhibitor.

Original languageEnglish
Pages (from-to)104522
JournalFitoterapia
Volume142
DOIs
Publication statusPublished - 2020 Apr
Externally publishedYes

Subject classification (UKÄ)

  • Medicinal Chemistry

Free keywords

  • Drug Evaluation, Preclinical
  • Endophytes/chemistry
  • Glycoside Hydrolase Inhibitors/chemistry
  • Juniperus/microbiology
  • Penicillium/chemistry
  • Xanthones/chemistry

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