Faezeh Zoghi-Paydar, Mahdiyeh Derakhshideh, Mohammad Azimi, Ahmad Ebadi, Gholamabbas Chehardoli, Mohammad Ali Faramarzi, Somayeh Mojtabavi, Mohammad Mahdavi, Zahra Najafi
{"title":"新型间苯二酚基2-氨基-4 -铬-3-碳腈衍生物α-葡萄糖苷酶抑制剂:合成、体外评价和分子动力学模拟研究","authors":"Faezeh Zoghi-Paydar, Mahdiyeh Derakhshideh, Mohammad Azimi, Ahmad Ebadi, Gholamabbas Chehardoli, Mohammad Ali Faramarzi, Somayeh Mojtabavi, Mohammad Mahdavi, Zahra Najafi","doi":"10.1002/ajoc.202500430","DOIUrl":null,"url":null,"abstract":"<p>A novel series of resorcinol-based 2-amino-4<i>H</i>-chromene-3-carbonitrile derivatives was synthesized and assessed against yeast α-glucosidase enzyme. All synthesized compounds showed significant inhibitory activities toward the enzyme with IC<sub>50</sub> values ranging from 44.0 ± 1.2 to 551.5 ± 1.6 µM in comparison with acarbose, as a standard agent (IC<sub>50</sub> = 750.0 µM). Among them, 2-amino-4-(4-((4-bromobenzyl)oxy)-3-methoxyphenyl)-7-hydroxy-4H-chromene-3-carbonitrile (<b>6e</b>) indicated the most potent inhibitory activity. The kinetic study indicated that the compound <b>6e</b> acts as a competitive α-glucosidase inhibitor. Afterward, molecular docking and molecular dynamics (MD) simulations of the <i>R</i>- and <i>S</i>-enantiomers of compound <b>6e</b> against a homology-modeled enzyme confirmed significant interactions with the catalytic residues. Additionally, in silico ADMET predictions showed that resorcinol-based 2-amino-4<i>H</i>-chromene-3-carbonitrile derivatives possess acceptable pharmacokinetic properties and therapeutic potential for the future treatment of type 2 diabetes mellitus (T2DM).</p>","PeriodicalId":130,"journal":{"name":"Asian Journal of Organic Chemistry","volume":"14 9","pages":""},"PeriodicalIF":2.7000,"publicationDate":"2025-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Novel Resorcinol-Based 2-Amino-4H-chromene-3-carbonitrile Derivatives as α-Glucosidase Inhibitors: Synthesis, In Vitro Evaluation, and Molecular Dynamics Simulation Studies\",\"authors\":\"Faezeh Zoghi-Paydar, Mahdiyeh Derakhshideh, Mohammad Azimi, Ahmad Ebadi, Gholamabbas Chehardoli, Mohammad Ali Faramarzi, Somayeh Mojtabavi, Mohammad Mahdavi, Zahra Najafi\",\"doi\":\"10.1002/ajoc.202500430\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>A novel series of resorcinol-based 2-amino-4<i>H</i>-chromene-3-carbonitrile derivatives was synthesized and assessed against yeast α-glucosidase enzyme. All synthesized compounds showed significant inhibitory activities toward the enzyme with IC<sub>50</sub> values ranging from 44.0 ± 1.2 to 551.5 ± 1.6 µM in comparison with acarbose, as a standard agent (IC<sub>50</sub> = 750.0 µM). Among them, 2-amino-4-(4-((4-bromobenzyl)oxy)-3-methoxyphenyl)-7-hydroxy-4H-chromene-3-carbonitrile (<b>6e</b>) indicated the most potent inhibitory activity. The kinetic study indicated that the compound <b>6e</b> acts as a competitive α-glucosidase inhibitor. Afterward, molecular docking and molecular dynamics (MD) simulations of the <i>R</i>- and <i>S</i>-enantiomers of compound <b>6e</b> against a homology-modeled enzyme confirmed significant interactions with the catalytic residues. Additionally, in silico ADMET predictions showed that resorcinol-based 2-amino-4<i>H</i>-chromene-3-carbonitrile derivatives possess acceptable pharmacokinetic properties and therapeutic potential for the future treatment of type 2 diabetes mellitus (T2DM).</p>\",\"PeriodicalId\":130,\"journal\":{\"name\":\"Asian Journal of Organic Chemistry\",\"volume\":\"14 9\",\"pages\":\"\"},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2025-07-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Asian Journal of Organic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://aces.onlinelibrary.wiley.com/doi/10.1002/ajoc.202500430\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Asian Journal of Organic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://aces.onlinelibrary.wiley.com/doi/10.1002/ajoc.202500430","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Novel Resorcinol-Based 2-Amino-4H-chromene-3-carbonitrile Derivatives as α-Glucosidase Inhibitors: Synthesis, In Vitro Evaluation, and Molecular Dynamics Simulation Studies
A novel series of resorcinol-based 2-amino-4H-chromene-3-carbonitrile derivatives was synthesized and assessed against yeast α-glucosidase enzyme. All synthesized compounds showed significant inhibitory activities toward the enzyme with IC50 values ranging from 44.0 ± 1.2 to 551.5 ± 1.6 µM in comparison with acarbose, as a standard agent (IC50 = 750.0 µM). Among them, 2-amino-4-(4-((4-bromobenzyl)oxy)-3-methoxyphenyl)-7-hydroxy-4H-chromene-3-carbonitrile (6e) indicated the most potent inhibitory activity. The kinetic study indicated that the compound 6e acts as a competitive α-glucosidase inhibitor. Afterward, molecular docking and molecular dynamics (MD) simulations of the R- and S-enantiomers of compound 6e against a homology-modeled enzyme confirmed significant interactions with the catalytic residues. Additionally, in silico ADMET predictions showed that resorcinol-based 2-amino-4H-chromene-3-carbonitrile derivatives possess acceptable pharmacokinetic properties and therapeutic potential for the future treatment of type 2 diabetes mellitus (T2DM).
期刊介绍:
Organic chemistry is the fundamental science that stands at the heart of chemistry, biology, and materials science. Research in these areas is vigorous and truly international, with three major regions making almost equal contributions: America, Europe and Asia. Asia now has its own top international organic chemistry journal—the Asian Journal of Organic Chemistry (AsianJOC)
The AsianJOC is designed to be a top-ranked international research journal and publishes primary research as well as critical secondary information from authors across the world. The journal covers organic chemistry in its entirety. Authors and readers come from academia, the chemical industry, and government laboratories.