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  2. Dimethylallylated stilbenoids by chemo-selective prenyltransferases and their α-glucosidase inhibitory effects

Dimethylallylated stilbenoids by chemo-selective prenyltransferases and their α-glucosidase inhibitory effects

  • Bioorg Chem. 2025 Apr:157:108261. doi: 10.1016/j.bioorg.2025.108261.
Min Yang 1 Jun Jin 2 Jiale Yi 3 Xia Yu 3 Chun-Mao Yuan 4 Kang Zhou 5
Affiliations

Affiliations

  • 1 School of Pharmaceutical Sciences, Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region, Ministry of Education, Guizhou University, Guiyang 550025, China.
  • 2 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China. Electronic address: 821892633@qq.com.
  • 3 Xiangya School of Pharmaceutical Sciences, Central South University, Changsha 410013, China.
  • 4 State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China. Electronic address: yuanchunmao01@126.com.
  • 5 School of Pharmaceutical Sciences, Key Laboratory of Plant Resource Conservation and Germplasm Innovation in Mountainous Region, Ministry of Education, Guizhou University, Guiyang 550025, China; State Key Laboratory of Functions and Applications of Medicinal Plants, Guizhou Medical University, Guiyang 550014, China. Electronic address: kangzhouzj@126.com.
Abstract

Prenylated stilbenoids are known for their unique health benefits and have been found to exhibit strong α-glucosidase inhibitory activities. In this study, the dimethylallylation of eight stilbenoids was investigated, which was catalyzed by engineered Enzymes of the Fungal prenyltransferase AnaPT. These reactions of stilbenoids catalyzed by AnaPT_F265D and AnaPT_F265G are chemo-selective and 17 products are all C-dimethylallylated stilbenoids, including twelve mono- and five di-dimethylallylated stilbenoids, significantly expanding the structure diversity of naturally occurring dimethylallylated stilbenoids. 10 Compounds were reported for the first time in this study. The molecular docking of 1D1 with AnaPT was also conducted, which revealed that N115 was likely a key residue. Our results showed that the catalytic efficiencies of AnaPT_F265D_N115K and AnaPT_F265D_N115A were higher than the Other mutants obtained. Eight compounds (1D1, 2D1, 3D2-3D4, 6D1, 6D4, and 8D1) exhibited inhibitory effects on α-glucosidase with IC50 values ranging from 5.43 ± 0.16 to 42.61 ± 0.17 μM. Among them, compound 8D1 with IC50 value of 5.43 ± 0.16 μM showed about 40 times stronger than the positive control, acarbose with an IC50 of 217.07 ± 1.92 μM in α-glucosidase inhibitory assays. These fundings not only enrich the structure diversity of dimethylallylated stilbenoids but also lay the foundation for the discovery of potential candidate compounds for the treatment of diabetes and anti-obesity drugs.

Keywords

AnaPT; Dimethylallylation; Prenyltransferases; Saturation mutagenesis; Stilbenoids; α-Glucosidase inhibitory activity.

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