{"title":"一些 3-hydroxypyridin-4-one 杂交化合物与酰基腙衍生物的设计、合成、硅 ADME、DFT、分子动力学模拟、抗酪氨酸酶和抗氧化活性。","authors":"Razieh Fazel, Bahareh Hassani, Fateme Zare, Habibollah Jokar Darzi, Mehdi Khoshneviszadeh, Alireza Poustforoosh, Marzieh Behrouz, Razieh Sabet, Hossein Sadeghpour","doi":"10.1080/07391102.2023.2252087","DOIUrl":null,"url":null,"abstract":"<p><p>Tyrosinase is the rate-limiting enzyme in synthesizing melanin. Melanin is responsible for changing the color of fruits and vegetables and protecting against skin photo-carcinogenesis. Herein, some of the hybrids of 3-hydroxypyridine-4-one and acylhydrazones were designed and synthesized to study the anti-tyrosinase and antioxidant activities. The diphenolase activity of mushroom tyrosinase using L-DOPA assayed the inhibitory effects, and the antioxidant activity was assessed using DPPH free radical. The synthesized derivatives were confirmed using <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, IR, and Mass spectroscopy. Among analogs, compound <b>5h</b> bearing furan ring with IC<sub>50</sub>=8.94 μM was more potent than kojic acid (IC<sub>50</sub>=16.68 μM). The pharmacokinetic profile of the compounds showed that the tested compounds had suitable oral bioavailability and drug-likeness properties. The molecular docking studies showed that compound <b>5h</b> was located in the tyrosinase-binding site. Also, the molecular dynamics simulation was performed on compound <b>5h</b>, proving the obtained molecular docking results. At the B3LYP/6-31 + G** level of theory, the reactivity descriptors for <b>5 g</b> and <b>5h</b> were investigated using DFT calculations. Also, IR frequency was calculated to verify DFT results with experimental data. The electrostatic potential energy of the surface and the HOMO and LUMO molecular orbitals were also studied. It agrees with experimental results that the <b>5h</b> is a soft molecule and ready for chemical reaction with other interacting molecules.Communicated by Ramaswamy H. Sarma.</p>","PeriodicalId":15272,"journal":{"name":"Journal of Biomolecular Structure & Dynamics","volume":null,"pages":null},"PeriodicalIF":2.7000,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Design, synthesis, <i>in silico</i> ADME, DFT, molecular dynamics simulation, anti-tyrosinase, and antioxidant activity of some of the 3-hydroxypyridin-4-one hybrids in combination with acylhydrazone derivatives.\",\"authors\":\"Razieh Fazel, Bahareh Hassani, Fateme Zare, Habibollah Jokar Darzi, Mehdi Khoshneviszadeh, Alireza Poustforoosh, Marzieh Behrouz, Razieh Sabet, Hossein Sadeghpour\",\"doi\":\"10.1080/07391102.2023.2252087\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Tyrosinase is the rate-limiting enzyme in synthesizing melanin. Melanin is responsible for changing the color of fruits and vegetables and protecting against skin photo-carcinogenesis. Herein, some of the hybrids of 3-hydroxypyridine-4-one and acylhydrazones were designed and synthesized to study the anti-tyrosinase and antioxidant activities. The diphenolase activity of mushroom tyrosinase using L-DOPA assayed the inhibitory effects, and the antioxidant activity was assessed using DPPH free radical. The synthesized derivatives were confirmed using <sup>1</sup>H-NMR, <sup>13</sup>C-NMR, IR, and Mass spectroscopy. Among analogs, compound <b>5h</b> bearing furan ring with IC<sub>50</sub>=8.94 μM was more potent than kojic acid (IC<sub>50</sub>=16.68 μM). The pharmacokinetic profile of the compounds showed that the tested compounds had suitable oral bioavailability and drug-likeness properties. The molecular docking studies showed that compound <b>5h</b> was located in the tyrosinase-binding site. Also, the molecular dynamics simulation was performed on compound <b>5h</b>, proving the obtained molecular docking results. At the B3LYP/6-31 + G** level of theory, the reactivity descriptors for <b>5 g</b> and <b>5h</b> were investigated using DFT calculations. Also, IR frequency was calculated to verify DFT results with experimental data. The electrostatic potential energy of the surface and the HOMO and LUMO molecular orbitals were also studied. It agrees with experimental results that the <b>5h</b> is a soft molecule and ready for chemical reaction with other interacting molecules.Communicated by Ramaswamy H. Sarma.</p>\",\"PeriodicalId\":15272,\"journal\":{\"name\":\"Journal of Biomolecular Structure & Dynamics\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.7000,\"publicationDate\":\"2024-11-01\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Journal of Biomolecular Structure & Dynamics\",\"FirstCategoryId\":\"99\",\"ListUrlMain\":\"https://doi.org/10.1080/07391102.2023.2252087\",\"RegionNum\":3,\"RegionCategory\":\"生物学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"2023/9/7 0:00:00\",\"PubModel\":\"Epub\",\"JCR\":\"Q3\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of Biomolecular Structure & Dynamics","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/07391102.2023.2252087","RegionNum":3,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/9/7 0:00:00","PubModel":"Epub","JCR":"Q3","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
酪氨酸酶是合成黑色素的限速酶。黑色素负责改变水果和蔬菜的颜色,防止皮肤光致癌。本文设计并合成了一些3-羟基吡啶-4-酮和酰基腙的杂种化合物,研究了它们的抗酪氨酸酶和抗氧化活性。L-DOPA法测定蘑菇酪氨酸酶二酚酶活性,DPPH自由基法测定其抗氧化活性。合成的衍生物经1H-NMR、13C-NMR、IR和质谱确证。在类似物中,含呋喃环(IC50= 8.94 μM)的化合物5h的效价高于含曲酸(IC50=16.68 μM)。化合物的药动学分析表明,化合物具有良好的口服生物利用度和药物相似性。分子对接研究表明,化合物5h位于酪氨酸酶结合位点。并对化合物5h进行了分子动力学模拟,验证了所得分子对接结果。在B3LYP/6-31 + G**理论水平上,用DFT计算研究了5g和5h的反应性描述符。计算了红外频率,用实验数据验证了DFT结果。研究了表面静电势能、HOMO和LUMO分子轨道。与实验结果一致,5h是一个软分子,可以与其他相互作用的分子发生化学反应。由Ramaswamy H. Sarma传达。
Design, synthesis, in silico ADME, DFT, molecular dynamics simulation, anti-tyrosinase, and antioxidant activity of some of the 3-hydroxypyridin-4-one hybrids in combination with acylhydrazone derivatives.
Tyrosinase is the rate-limiting enzyme in synthesizing melanin. Melanin is responsible for changing the color of fruits and vegetables and protecting against skin photo-carcinogenesis. Herein, some of the hybrids of 3-hydroxypyridine-4-one and acylhydrazones were designed and synthesized to study the anti-tyrosinase and antioxidant activities. The diphenolase activity of mushroom tyrosinase using L-DOPA assayed the inhibitory effects, and the antioxidant activity was assessed using DPPH free radical. The synthesized derivatives were confirmed using 1H-NMR, 13C-NMR, IR, and Mass spectroscopy. Among analogs, compound 5h bearing furan ring with IC50=8.94 μM was more potent than kojic acid (IC50=16.68 μM). The pharmacokinetic profile of the compounds showed that the tested compounds had suitable oral bioavailability and drug-likeness properties. The molecular docking studies showed that compound 5h was located in the tyrosinase-binding site. Also, the molecular dynamics simulation was performed on compound 5h, proving the obtained molecular docking results. At the B3LYP/6-31 + G** level of theory, the reactivity descriptors for 5 g and 5h were investigated using DFT calculations. Also, IR frequency was calculated to verify DFT results with experimental data. The electrostatic potential energy of the surface and the HOMO and LUMO molecular orbitals were also studied. It agrees with experimental results that the 5h is a soft molecule and ready for chemical reaction with other interacting molecules.Communicated by Ramaswamy H. Sarma.
期刊介绍:
The Journal of Biomolecular Structure and Dynamics welcomes manuscripts on biological structure, dynamics, interactions and expression. The Journal is one of the leading publications in high end computational science, atomic structural biology, bioinformatics, virtual drug design, genomics and biological networks.