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Varic acid analogues from fungus as PTP1B inhibitors: Biological evaluation and structure-activity relationships
Wenlong Sun1, Chunlin Zhuang2, Xia Li1
1School of Life Science, Biotechnology, Dalian University of Technology, Dalian, Liaoning 116024, China.
Abstract:
Protein tyrosine phosphatase 1B (PTP1B) inhibitors as potential therapies for diabetes and obesity have attracted much attention in recent years. Six varic acid analogues were isolated from two strains of fungi and evaluated for PTP1B inhibition activities. The structure-activity relationships were also characterized and predicted by molecular modeling. Further kinetic studies indicated the reversible and competitive inhibition manner of varic acid analogues. Trivaric acid showed insulin-sensitizing effect not only in vitro but also in vivo, representing a promising lead compound for further optimization.
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