Min Yang , Jun Jin , Jiale Yi , Xia Yu , Chun-Mao Yuan , Kang Zhou
{"title":"Dimethylallylated stilbenoids by chemo-selective prenyltransferases and their α-glucosidase inhibitory effects","authors":"Min Yang , Jun Jin , Jiale Yi , Xia Yu , Chun-Mao Yuan , Kang Zhou","doi":"10.1016/j.bioorg.2025.108261","DOIUrl":null,"url":null,"abstract":"<div><div>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 <em>C</em>-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 <strong>1D1</strong> 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 (<strong>1D1</strong>, <strong>2D1</strong>, <strong>3D2</strong>–<strong>3D4</strong>, <strong>6D1</strong>, <strong>6D4</strong>, and <strong>8D1</strong>) exhibited inhibitory effects on α-glucosidase with IC<sub>50</sub> values ranging from 5.43 ± 0.16 to 42.61 ± 0.17 μM. Among them, compound <strong>8D1</strong> with IC<sub>50</sub> value of 5.43 ± 0.16 μM showed about 40 times stronger than the positive control, acarbose with an IC<sub>50</sub> 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.</div></div>","PeriodicalId":257,"journal":{"name":"Bioorganic Chemistry","volume":"157 ","pages":"Article 108261"},"PeriodicalIF":4.7000,"publicationDate":"2025-02-07","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0045206825001415","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
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.
期刊介绍：
Bioorganic Chemistry publishes research that addresses biological questions at the molecular level, using organic chemistry and principles of physical organic chemistry. The scope of the journal covers a range of topics at the organic chemistry-biology interface, including: enzyme catalysis, biotransformation and enzyme inhibition; nucleic acids chemistry; medicinal chemistry; natural product chemistry, natural product synthesis and natural product biosynthesis; antimicrobial agents; lipid and peptide chemistry; biophysical chemistry; biological probes; bio-orthogonal chemistry and biomimetic chemistry.
For manuscripts dealing with synthetic bioactive compounds, the Journal requires that the molecular target of the compounds described must be known, and must be demonstrated experimentally in the manuscript. For studies involving natural products, if the molecular target is unknown, some data beyond simple cell-based toxicity studies to provide insight into the mechanism of action is required. Studies supported by molecular docking are welcome, but must be supported by experimental data. The Journal does not consider manuscripts that are purely theoretical or computational in nature.
The Journal publishes regular articles, short communications and reviews. Reviews are normally invited by Editors or Editorial Board members. Authors of unsolicited reviews should first contact an Editor or Editorial Board member to determine whether the proposed article is within the scope of the Journal.
京公网安备 11010802042870号
京ICP备2023020795号-1
分享
求助内容：
应助结果提醒方式：
扫码关注我们
