Protein tyrosine phosphatase 1B(PTP1B) inhibitors from Arnebia euchroma / 中国药学杂志

ABSTRACT

OBJECTIVE: To study the chemical constituents of the extract of Arnebia euchroma (Royle) Johnst. and screen natural protein tyrosine phosphatase 1B (PTP1B) inhibitors. METHODS: Silica gel, MCI gel, ODS gel, and Sephadex LH-20 chromatographic techniques were used to study the chemical constituents of A. euchroma, the chemical structures were elucidated by analysis of physico-chemical and spectral data, and the inhibitory activity on PTP1B enzyme was tested in vitro. RESULTS: Eight compounds were obtained and their structures were identified as deoxyshikonin (1), shikonin (2), acetylshikonin (3), β, β'-dimethylacrylalkannin (4), quercetin (5), kaempferol (6), kaempferide (7), and β-sitosterol (8). Compounds 1-4 exhibited inhibitory activities on PTP1B with IC50 values of (0.80±0.16), (4.42±0.37), (1.02±0.13), and (0.36±0.08) μmol·L-1, respectively. The study of structure-activity relationship showed that the ring of naphthoquinone might be the key skeleton structure for the inhibition activity on PTP1B, and the 2-substituted long lipo-chain of naphthoquinone significantly affected the activity of these compounds the increase in the polarity of the lipo-chain led to the reduction of activity, while the increase in the terminal double bond of the lipo-chain led to the enhancement of activity. CONCLUSION: Shikonin derivatives with 1, 4-naphthoquinone skeleton is a new type of leading compounds for the treatment of diabetes.