Nehal A E Youssef, Yasser A Selim, Lina A Shaheen, Ahmed A Fadda, Hatem E Gaffer, Sherihan A El-Hadidy
{"title":"潜在活性细胞毒性药物香豆素环上新型吡啶嘧啶基团的设计与合成及其对接研究。","authors":"Nehal A E Youssef, Yasser A Selim, Lina A Shaheen, Ahmed A Fadda, Hatem E Gaffer, Sherihan A El-Hadidy","doi":"10.1038/s41598-025-05325-1","DOIUrl":null,"url":null,"abstract":"<p><p>Many pyridopyrimidine moieties linked to the coumarin ring were synthesized by the reaction of malononitrile with 7-hydroxy-4-methyl-2-oxo-2 H-chromene-8-carbaldehyde (2) directly in the presence of ammonium acetate and different ketones and studied the effect of other basic catalysis, ratio of reactants and the effect of the solvent. The newly synthesized compounds were evaluated for their cytotoxic activity against four cell lines namely HepG2, WI-38, VERO, and MCF-7. The cytotoxic activity showed that compounds 8, 9, 10, and 7 have the highest activity against the studied cell lines. Focusing on the binding affinity and interactions between the five synthesized derivatives with the highest anticancer activity and specific amino acids of 4HJO residues over the molecular docking analysis. Derivative 10 recorded the highest energy score with good RMSD compared to the rest of the derivatives.</p>","PeriodicalId":21811,"journal":{"name":"Scientific Reports","volume":"15 1","pages":"20155"},"PeriodicalIF":3.9000,"publicationDate":"2025-06-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181260/pdf/","citationCount":"0","resultStr":"{\"title\":\"Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study.\",\"authors\":\"Nehal A E Youssef, Yasser A Selim, Lina A Shaheen, Ahmed A Fadda, Hatem E Gaffer, Sherihan A El-Hadidy\",\"doi\":\"10.1038/s41598-025-05325-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>Many pyridopyrimidine moieties linked to the coumarin ring were synthesized by the reaction of malononitrile with 7-hydroxy-4-methyl-2-oxo-2 H-chromene-8-carbaldehyde (2) directly in the presence of ammonium acetate and different ketones and studied the effect of other basic catalysis, ratio of reactants and the effect of the solvent. The newly synthesized compounds were evaluated for their cytotoxic activity against four cell lines namely HepG2, WI-38, VERO, and MCF-7. The cytotoxic activity showed that compounds 8, 9, 10, and 7 have the highest activity against the studied cell lines. Focusing on the binding affinity and interactions between the five synthesized derivatives with the highest anticancer activity and specific amino acids of 4HJO residues over the molecular docking analysis. Derivative 10 recorded the highest energy score with good RMSD compared to the rest of the derivatives.</p>\",\"PeriodicalId\":21811,\"journal\":{\"name\":\"Scientific Reports\",\"volume\":\"15 1\",\"pages\":\"20155\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-06-20\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12181260/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Scientific Reports\",\"FirstCategoryId\":\"103\",\"ListUrlMain\":\"https://doi.org/10.1038/s41598-025-05325-1\",\"RegionNum\":2,\"RegionCategory\":\"综合性期刊\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"MULTIDISCIPLINARY SCIENCES\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Scientific Reports","FirstCategoryId":"103","ListUrlMain":"https://doi.org/10.1038/s41598-025-05325-1","RegionNum":2,"RegionCategory":"综合性期刊","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"MULTIDISCIPLINARY SCIENCES","Score":null,"Total":0}
引用次数: 0
摘要
采用丙二腈与7-羟基-4-甲基-2-氧-2- h -铬-8-乙醛(2)在乙酸铵和不同酮类存在下直接反应合成了香豆素环上的多个吡啶嘧啶基团，并研究了其他碱催化、反应物配比和溶剂的影响。新合成的化合物对HepG2、WI-38、VERO和MCF-7四种细胞系的细胞毒活性进行了评价。细胞毒活性表明，化合物8、9、10和7对所研究的细胞系的细胞毒活性最高。通过分子对接分析，重点研究合成的抗癌活性最高的5个衍生物与4HJO残基特定氨基酸之间的结合亲和力和相互作用。与其他衍生品相比，衍生品10的能量得分最高，RMSD良好。
Design and synthesis of novel pyridopyrimidine moieties linked to coumarin ring of potentially active cytotoxic agents and their docking study.
Many pyridopyrimidine moieties linked to the coumarin ring were synthesized by the reaction of malononitrile with 7-hydroxy-4-methyl-2-oxo-2 H-chromene-8-carbaldehyde (2) directly in the presence of ammonium acetate and different ketones and studied the effect of other basic catalysis, ratio of reactants and the effect of the solvent. The newly synthesized compounds were evaluated for their cytotoxic activity against four cell lines namely HepG2, WI-38, VERO, and MCF-7. The cytotoxic activity showed that compounds 8, 9, 10, and 7 have the highest activity against the studied cell lines. Focusing on the binding affinity and interactions between the five synthesized derivatives with the highest anticancer activity and specific amino acids of 4HJO residues over the molecular docking analysis. Derivative 10 recorded the highest energy score with good RMSD compared to the rest of the derivatives.
期刊介绍：
We publish original research from all areas of the natural sciences, psychology, medicine and engineering. You can learn more about what we publish by browsing our specific scientific subject areas below or explore Scientific Reports by browsing all articles and collections.
Scientific Reports has a 2-year impact factor: 4.380 (2021), and is the 6th most-cited journal in the world, with more than 540,000 citations in 2020 (Clarivate Analytics, 2021).
•Engineering
Engineering covers all aspects of engineering, technology, and applied science. It plays a crucial role in the development of technologies to address some of the world''s biggest challenges, helping to save lives and improve the way we live.
•Physical sciences
Physical sciences are those academic disciplines that aim to uncover the underlying laws of nature — often written in the language of mathematics. It is a collective term for areas of study including astronomy, chemistry, materials science and physics.
•Earth and environmental sciences
Earth and environmental sciences cover all aspects of Earth and planetary science and broadly encompass solid Earth processes, surface and atmospheric dynamics, Earth system history, climate and climate change, marine and freshwater systems, and ecology. It also considers the interactions between humans and these systems.
•Biological sciences
Biological sciences encompass all the divisions of natural sciences examining various aspects of vital processes. The concept includes anatomy, physiology, cell biology, biochemistry and biophysics, and covers all organisms from microorganisms, animals to plants.
•Health sciences
The health sciences study health, disease and healthcare. This field of study aims to develop knowledge, interventions and technology for use in healthcare to improve the treatment of patients.
求助内容：
应助结果提醒方式：
京公网安备 11010802042870号
