Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling
Abstract Arylamine N-acetyltransferases (NATs, E.C. 2.3.1.5) constitute a family of phase II drug metabolizing enzymes. These enzymes catalyze the transfer of acetyl groups from acetyl-CoA to a variety of substrates including arylamines, arylhydrazines, and N-hydroxyarylamines. By facilitating these...
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Nature Portfolio
2025-01-01
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| Online Access: | https://doi.org/10.1038/s41598-025-85869-4 |
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| author | Wei Wei Xionghao Li Ning Hou Aowei Xie Huicong Liang Ting Gao Xiaoli Jing Liqin Li Jiejie Hao Ximing Xu |
| author_facet | Wei Wei Xionghao Li Ning Hou Aowei Xie Huicong Liang Ting Gao Xiaoli Jing Liqin Li Jiejie Hao Ximing Xu |
| author_sort | Wei Wei |
| collection | DOAJ |
| description | Abstract Arylamine N-acetyltransferases (NATs, E.C. 2.3.1.5) constitute a family of phase II drug metabolizing enzymes. These enzymes catalyze the transfer of acetyl groups from acetyl-CoA to a variety of substrates including arylamines, arylhydrazines, and N-hydroxyarylamines. By facilitating these reactions, NATs play a pivotal role in the detoxification and metabolic processing of a wide range of drugs and carcinogens. NAT in marine V. vulnificus plays a role in the metabolism of drugs, leading to the development of drug resistance in marine V. vulnificus. However, inhibitors targeted marine V. vulnificus NAT [(VIBVN)NAT] remain unclear. Therefore, our research aimed to identify potential hit compounds that target (VIBVN)NAT. We integrated multiple computational approaches to screen for effective inhibitors. From this process, we identified two hit compounds, AK-968-11563024 and AG-205-36710025, with IC50 values of 18.86 µM and 33.27 µM, respectively. Molecular dynamics simulations further elucidated the binding mechanism between (VIBVN)NAT and AK-968-11563024. Our study revealed that AK-968-11563024 forms stable interactions with PHE124, HIS167, and TRP230, which may contribute to its biological activity. Our findings provide a valuable foundation for the future development of drugs targeted therapeutics against (VIBVN)NAT. |
| format | Article |
| id | doaj-art-be953ef46489455ca4c91607d336d71a |
| institution | Kabale University |
| issn | 2045-2322 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Scientific Reports |
| spelling | doaj-art-be953ef46489455ca4c91607d336d71a2025-01-26T12:28:18ZengNature PortfolioScientific Reports2045-23222025-01-0115111110.1038/s41598-025-85869-4Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modelingWei Wei0Xionghao Li1Ning Hou2Aowei Xie3Huicong Liang4Ting Gao5Xiaoli Jing6Liqin Li7Jiejie Hao8Ximing Xu9Affiliated Huzhou Hospital, The Key Laboratory of Molecular Medicine, Zhejiang University School of Medicine, Huzhou Central Hospital, The Fifth School of Clinical Medicine of Zhejiang Chinese Medical UniversityKey Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ministry of Education, Ocean University of ChinaKey Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ministry of Education, Ocean University of ChinaCollege of Food Science and Engineering, Ocean University of ChinaKey Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ministry of Education, Ocean University of ChinaCollege of Food Science and Engineering, Ocean University of ChinaNetwork and Information Center, Qingdao Marine Science and Technology CenterAffiliated Huzhou Hospital, The Key Laboratory of Molecular Medicine, Zhejiang University School of Medicine, Huzhou Central Hospital, The Fifth School of Clinical Medicine of Zhejiang Chinese Medical UniversityKey Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ministry of Education, Ocean University of ChinaKey Laboratory of Marine Drugs, School of Medicine and Pharmacy, Ministry of Education, Ocean University of ChinaAbstract Arylamine N-acetyltransferases (NATs, E.C. 2.3.1.5) constitute a family of phase II drug metabolizing enzymes. These enzymes catalyze the transfer of acetyl groups from acetyl-CoA to a variety of substrates including arylamines, arylhydrazines, and N-hydroxyarylamines. By facilitating these reactions, NATs play a pivotal role in the detoxification and metabolic processing of a wide range of drugs and carcinogens. NAT in marine V. vulnificus plays a role in the metabolism of drugs, leading to the development of drug resistance in marine V. vulnificus. However, inhibitors targeted marine V. vulnificus NAT [(VIBVN)NAT] remain unclear. Therefore, our research aimed to identify potential hit compounds that target (VIBVN)NAT. We integrated multiple computational approaches to screen for effective inhibitors. From this process, we identified two hit compounds, AK-968-11563024 and AG-205-36710025, with IC50 values of 18.86 µM and 33.27 µM, respectively. Molecular dynamics simulations further elucidated the binding mechanism between (VIBVN)NAT and AK-968-11563024. Our study revealed that AK-968-11563024 forms stable interactions with PHE124, HIS167, and TRP230, which may contribute to its biological activity. Our findings provide a valuable foundation for the future development of drugs targeted therapeutics against (VIBVN)NAT.https://doi.org/10.1038/s41598-025-85869-4 |
| spellingShingle | Wei Wei Xionghao Li Ning Hou Aowei Xie Huicong Liang Ting Gao Xiaoli Jing Liqin Li Jiejie Hao Ximing Xu Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling Scientific Reports |
| title | Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling |
| title_full | Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling |
| title_fullStr | Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling |
| title_full_unstemmed | Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling |
| title_short | Novel inhibitors of the (VIBVN) NAT protein identified through pharmacophore modeling |
| title_sort | novel inhibitors of the vibvn nat protein identified through pharmacophore modeling |
| url | https://doi.org/10.1038/s41598-025-85869-4 |
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