探索吲哚-恶二唑苯甲酰胺混合物作为酪氨酸酶抑制剂的机理:线性-布尔克图谱分析和计算研究的启示

IF 1.1 4区 化学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
M. Nazir, U. Khan, M. Jahangir, K. Hayat, S. A. R. Bokhari, A. Shakoor, E. Ahmad, H. M. F. Haider
{"title":"探索吲哚-恶二唑苯甲酰胺混合物作为酪氨酸酶抑制剂的机理:线性-布尔克图谱分析和计算研究的启示","authors":"M. Nazir,&nbsp;U. Khan,&nbsp;M. Jahangir,&nbsp;K. Hayat,&nbsp;S. A. R. Bokhari,&nbsp;A. Shakoor,&nbsp;E. Ahmad,&nbsp;H. M. F. Haider","doi":"10.1134/S106816202406013X","DOIUrl":null,"url":null,"abstract":"<p><b>Objective:</b> This study aimed to synthesize hybrid compounds incorporating indole, oxadiazole, and benzamide moieties, leveraging their known biological activities, to evaluate their potential as tyrosinase inhibitors.<b> Methods:</b> A convergent synthetic approach was employed to develop the hybrid compounds. Structural confirmation was achieved through infrared spectroscopy (IR), proton nuclear magnetic resonance (<sup>1</sup>H NMR), carbon nuclear magnetic resonance (<sup>13</sup>C NMR), and elemental analysis (CHN). The inhibitory effects on tyrosinase were assessed using enzyme kinetics, with Lineweaver-Burk plots utilized to determine the mechanism of inhibition.<b> Results and Discussion:</b> The synthesized bi-heterocyclic benzamides demonstrated excellent inhibitory activities against tyrosinase compared to the standard control. Compound (<b>VIIIf</b>) exhibited non-competitive inhibition, forming an enzyme-inhibitor complex, with an inhibition constant (<i>K</i><sub>i</sub>) of 0.0033 µM. Computational analysis indicated favorable binding energy values for these compounds. The study highlights the promising potential of these hybrid molecules as effective tyrosinase inhibitors. The structure-activity relationship analysis suggests that the incorporation of indole, oxadiazole, and benzamide moieties enhances the inhibitory efficacy against tyrosinase, which is crucial for developing treatments for skin disorders.<b> Conclusions:</b> The synthesized indole-oxadiazole-benzamide hybrids are identified as potent tyrosinase inhibitors with significant potential as medicinal scaffolds for treating skin conditions. Further investigations into their therapeutic applications are warranted.</p>","PeriodicalId":758,"journal":{"name":"Russian Journal of Bioorganic Chemistry","volume":"50 6","pages":"2325 - 2343"},"PeriodicalIF":1.1000,"publicationDate":"2024-12-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Exploring the Mechanisms of Indole-Oxadiazole Benzamide Hybrids as Tyrosinase Inhibitors: Insights from Lineweaver-Burk Plot Analysis and Computational Studies\",\"authors\":\"M. Nazir,&nbsp;U. Khan,&nbsp;M. Jahangir,&nbsp;K. Hayat,&nbsp;S. A. R. Bokhari,&nbsp;A. Shakoor,&nbsp;E. Ahmad,&nbsp;H. M. F. Haider\",\"doi\":\"10.1134/S106816202406013X\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><b>Objective:</b> This study aimed to synthesize hybrid compounds incorporating indole, oxadiazole, and benzamide moieties, leveraging their known biological activities, to evaluate their potential as tyrosinase inhibitors.<b> Methods:</b> A convergent synthetic approach was employed to develop the hybrid compounds. Structural confirmation was achieved through infrared spectroscopy (IR), proton nuclear magnetic resonance (<sup>1</sup>H NMR), carbon nuclear magnetic resonance (<sup>13</sup>C NMR), and elemental analysis (CHN). The inhibitory effects on tyrosinase were assessed using enzyme kinetics, with Lineweaver-Burk plots utilized to determine the mechanism of inhibition.<b> Results and Discussion:</b> The synthesized bi-heterocyclic benzamides demonstrated excellent inhibitory activities against tyrosinase compared to the standard control. Compound (<b>VIIIf</b>) exhibited non-competitive inhibition, forming an enzyme-inhibitor complex, with an inhibition constant (<i>K</i><sub>i</sub>) of 0.0033 µM. Computational analysis indicated favorable binding energy values for these compounds. The study highlights the promising potential of these hybrid molecules as effective tyrosinase inhibitors. The structure-activity relationship analysis suggests that the incorporation of indole, oxadiazole, and benzamide moieties enhances the inhibitory efficacy against tyrosinase, which is crucial for developing treatments for skin disorders.<b> Conclusions:</b> The synthesized indole-oxadiazole-benzamide hybrids are identified as potent tyrosinase inhibitors with significant potential as medicinal scaffolds for treating skin conditions. Further investigations into their therapeutic applications are warranted.</p>\",\"PeriodicalId\":758,\"journal\":{\"name\":\"Russian Journal of Bioorganic Chemistry\",\"volume\":\"50 6\",\"pages\":\"2325 - 2343\"},\"PeriodicalIF\":1.1000,\"publicationDate\":\"2024-12-16\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Russian Journal of Bioorganic Chemistry\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://link.springer.com/article/10.1134/S106816202406013X\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q4\",\"JCRName\":\"BIOCHEMISTRY & MOLECULAR BIOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Russian Journal of Bioorganic Chemistry","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1134/S106816202406013X","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

摘要

目的:本研究旨在合成含有吲哚、恶二唑和苯甲酰胺基团的杂化化合物,利用它们已知的生物活性,评估它们作为酪氨酸酶抑制剂的潜力。方法:采用聚合合成方法制备杂化化合物。通过红外光谱(IR)、质子核磁共振(1H NMR)、碳核磁共振(13C NMR)和元素分析(CHN)进行结构确认。利用酶动力学方法评估其对酪氨酸酶的抑制作用,并利用Lineweaver-Burk图确定其抑制机制。结果与讨论:与标准对照相比,合成的双杂环苯酰胺具有较好的酪氨酸酶抑制活性。化合物(viii if)表现出非竞争性抑制,形成酶抑制剂复合物,抑制常数(Ki)为0.0033µM。计算分析表明这些化合物具有良好的结合能值。该研究强调了这些杂交分子作为有效酪氨酸酶抑制剂的潜力。构效关系分析表明,吲哚、恶二唑和苯酰胺部分的掺入增强了对酪氨酸酶的抑制作用,这对开发皮肤疾病的治疗方法至关重要。结论:合成的吲哚-恶二唑-苯甲酰胺杂合体是有效的酪氨酸酶抑制剂,具有作为治疗皮肤疾病的药物支架的巨大潜力。对其治疗应用的进一步研究是有必要的。
本文章由计算机程序翻译,如有差异,请以英文原文为准。

Exploring the Mechanisms of Indole-Oxadiazole Benzamide Hybrids as Tyrosinase Inhibitors: Insights from Lineweaver-Burk Plot Analysis and Computational Studies

Exploring the Mechanisms of Indole-Oxadiazole Benzamide Hybrids as Tyrosinase Inhibitors: Insights from Lineweaver-Burk Plot Analysis and Computational Studies

Objective: This study aimed to synthesize hybrid compounds incorporating indole, oxadiazole, and benzamide moieties, leveraging their known biological activities, to evaluate their potential as tyrosinase inhibitors. Methods: A convergent synthetic approach was employed to develop the hybrid compounds. Structural confirmation was achieved through infrared spectroscopy (IR), proton nuclear magnetic resonance (1H NMR), carbon nuclear magnetic resonance (13C NMR), and elemental analysis (CHN). The inhibitory effects on tyrosinase were assessed using enzyme kinetics, with Lineweaver-Burk plots utilized to determine the mechanism of inhibition. Results and Discussion: The synthesized bi-heterocyclic benzamides demonstrated excellent inhibitory activities against tyrosinase compared to the standard control. Compound (VIIIf) exhibited non-competitive inhibition, forming an enzyme-inhibitor complex, with an inhibition constant (Ki) of 0.0033 µM. Computational analysis indicated favorable binding energy values for these compounds. The study highlights the promising potential of these hybrid molecules as effective tyrosinase inhibitors. The structure-activity relationship analysis suggests that the incorporation of indole, oxadiazole, and benzamide moieties enhances the inhibitory efficacy against tyrosinase, which is crucial for developing treatments for skin disorders. Conclusions: The synthesized indole-oxadiazole-benzamide hybrids are identified as potent tyrosinase inhibitors with significant potential as medicinal scaffolds for treating skin conditions. Further investigations into their therapeutic applications are warranted.

求助全文
通过发布文献求助,成功后即可免费获取论文全文。 去求助
来源期刊
Russian Journal of Bioorganic Chemistry
Russian Journal of Bioorganic Chemistry 生物-生化与分子生物学
CiteScore
1.80
自引率
10.00%
发文量
118
审稿时长
3 months
期刊介绍: Russian Journal of Bioorganic Chemistry publishes reviews and original experimental and theoretical studies on the structure, function, structure–activity relationships, and synthesis of biopolymers, such as proteins, nucleic acids, polysaccharides, mixed biopolymers, and their complexes, and low-molecular-weight biologically active compounds (peptides, sugars, lipids, antibiotics, etc.). The journal also covers selected aspects of neuro- and immunochemistry, biotechnology, and ecology.
×
引用
GB/T 7714-2015
复制
MLA
复制
APA
复制
导出至
BibTeX EndNote RefMan NoteFirst NoteExpress
×
提示
您的信息不完整,为了账户安全,请先补充。
现在去补充
×
提示
您因"违规操作"
具体请查看互助需知
我知道了
×
提示
确定
请完成安全验证×
copy
已复制链接
快去分享给好友吧!
我知道了
右上角分享
点击右上角分享
0
联系我们:info@booksci.cn Book学术提供免费学术资源搜索服务,方便国内外学者检索中英文文献。致力于提供最便捷和优质的服务体验。 Copyright © 2023 布克学术 All rights reserved.
京ICP备2023020795号-1
ghs 京公网安备 11010802042870号
Book学术文献互助
Book学术文献互助群
群 号:481959085
Book学术官方微信