Synthesis of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives as potential anti-diabetic and anticancer agents.

IF 1.1 4区 生物学 Q4 BIOCHEMISTRY & MOLECULAR BIOLOGY
S H Sukanya, Talavara Venkatesh, H Shanavaz
{"title":"Synthesis of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1<i>H</i>,3<i>H</i>,5<i>H</i>)-trione derivatives as potential anti-diabetic and anticancer agents.","authors":"S H Sukanya, Talavara Venkatesh, H Shanavaz","doi":"10.1080/15257770.2023.2289479","DOIUrl":null,"url":null,"abstract":"<p><p>In this work, we developed a series of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1<i>H</i>,3<i>H</i>,5<i>H</i>)-trione derivatives <b>4(a-e)</b> <i>via</i> a one-pot multicomponent reaction. The structures of the compounds were confirmed using analytical and spectroscopic techniques. Also, the synthesized compounds were screened for their anti-diabetic activity, cytotoxicity and <i>in silico</i> studies. The activity results suggested that the compound <b>4e</b> exhibited least IC<sub>50</sub> values of 0.055 ± 0.002 µM, 0.050 ± 0.002 µM and 0.009 ± 0.001 µM for α-amylase, α-glucosidase and cytotoxicity respectively. Further, <i>in silico</i> molecular docking results revealed that all the obtained compounds effectively interacted with exo-β-D-glucosaminidase and P38 MAP kinase proteins with good binding energies. In that, <b>4e</b> compound established the least binding energy of -9.6 and -9.1 kcal/mol, respectively. Moreover, our synthesized compounds were subjected to ADME studies, which suggested that all the synthesized compounds obeyed all five rules with good bioavailability and were suitable as drug leads against anti-diabetic and anticancer treatment.</p>","PeriodicalId":19343,"journal":{"name":"Nucleosides, Nucleotides & Nucleic Acids","volume":" ","pages":"619-642"},"PeriodicalIF":1.1000,"publicationDate":"2024-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Nucleosides, Nucleotides & Nucleic Acids","FirstCategoryId":"99","ListUrlMain":"https://doi.org/10.1080/15257770.2023.2289479","RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"2023/12/6 0:00:00","PubModel":"Epub","JCR":"Q4","JCRName":"BIOCHEMISTRY & MOLECULAR BIOLOGY","Score":null,"Total":0}
引用次数: 0

Abstract

In this work, we developed a series of novel 5-[3-(4-chlorophenyl)-substituted-1,3-dimethylpyrimidine-2,4,6(1H,3H,5H)-trione derivatives 4(a-e) via a one-pot multicomponent reaction. The structures of the compounds were confirmed using analytical and spectroscopic techniques. Also, the synthesized compounds were screened for their anti-diabetic activity, cytotoxicity and in silico studies. The activity results suggested that the compound 4e exhibited least IC50 values of 0.055 ± 0.002 µM, 0.050 ± 0.002 µM and 0.009 ± 0.001 µM for α-amylase, α-glucosidase and cytotoxicity respectively. Further, in silico molecular docking results revealed that all the obtained compounds effectively interacted with exo-β-D-glucosaminidase and P38 MAP kinase proteins with good binding energies. In that, 4e compound established the least binding energy of -9.6 and -9.1 kcal/mol, respectively. Moreover, our synthesized compounds were subjected to ADME studies, which suggested that all the synthesized compounds obeyed all five rules with good bioavailability and were suitable as drug leads against anti-diabetic and anticancer treatment.

合成新型 5-[3-(4-氯苯基)-取代的-1,3-二甲基嘧啶-2,4,6(1H,3H,5H)-三酮衍生物,作为潜在的抗糖尿病和抗癌药物。
在这项工作中,我们通过一锅多组分反应开发了一系列新型 5-[3-(4-氯苯基)-取代的-1,3-二甲基嘧啶-2,4,6(1H,3H,5H)-三酮衍生物 4(a-e)。利用分析和光谱技术确认了这些化合物的结构。此外,还对合成的化合物进行了抗糖尿病活性、细胞毒性筛选和硅学研究。活性结果表明,化合物 4e 对 α-淀粉酶、α-葡萄糖苷酶和细胞毒性的 IC50 值分别为 0.055 ± 0.002 µM、0.050 ± 0.002 µM 和 0.009 ± 0.001 µM。此外,硅学分子对接结果显示,所有化合物都能有效地与外-β-D-葡萄糖苷酶和 P38 MAP 激酶蛋白相互作用,并具有良好的结合能。其中,4e化合物的结合能最低,分别为-9.6和-9.1 kcal/mol。此外,我们还对合成的化合物进行了 ADME 研究,结果表明所有合成的化合物都符合所有五项规则,具有良好的生物利用度,适合作为抗糖尿病和抗癌治疗的药物先导物。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
求助全文
约1分钟内获得全文 求助全文
来源期刊
Nucleosides, Nucleotides & Nucleic Acids
Nucleosides, Nucleotides & Nucleic Acids 生物-生化与分子生物学
CiteScore
2.60
自引率
7.70%
发文量
91
审稿时长
6 months
期刊介绍: Nucleosides, Nucleotides & Nucleic Acids publishes research articles, short notices, and concise, critical reviews of related topics that focus on the chemistry and biology of nucleosides, nucleotides, and nucleic acids. Complete with experimental details, this all-inclusive journal emphasizes the synthesis, biological activities, new and improved synthetic methods, and significant observations related to new compounds.
×
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