{"title":"取代喹啉衍生物的合成、抗癌评价、分子对接及DFT研究","authors":"İlbilge Merve Şenol, Begüm Nurpelin SAĞLIK Özkan, İlhami Çelik, Sultan Funda Ekti","doi":"10.1002/ardp.70078","DOIUrl":null,"url":null,"abstract":"<div>\n \n <p>Seven new quinoline derivatives with different functional groups at positions 2, 3, and 4 were synthesized and subsequently assessed for their biological activities. Four synthesized compounds exhibited significant cytotoxic effects against A549 and MCF7 cells. Compound <b>4f</b> demonstrated IC<sub>50</sub> values comparable to that of the standard drug doxorubicin and showed a similar selectivity profile, exhibiting low toxicity toward healthy NIH3T3 cells. Furthermore, compound <b>4f</b> displayed a strong EGFR inhibition profile with an IC<sub>50</sub> value of 0.015 ± 0.001 µM. Molecular docking studies revealed that <b>4f</b> forms strong interactions with key amino acids on the active site of EGFR. Additionally, DFT analyses were conducted to calculate dipole moments, HOMO-LUMO energy gaps, and molecular electrostatic potential maps. Theoretical and experimental NMR chemical shift values showed a high correlation and confirmed the consistency of the computational results. These results indicate the potential of quinoline derivatives, especially of compound <b>4f</b>, as promising candidates for the development of chemotherapeutic agents.</p></div>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":"358 8","pages":""},"PeriodicalIF":3.6000,"publicationDate":"2025-08-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis, Anticancer Evaluation, Molecular Docking, and DFT Studies of Substituted Quinoline Derivatives\",\"authors\":\"İlbilge Merve Şenol, Begüm Nurpelin SAĞLIK Özkan, İlhami Çelik, Sultan Funda Ekti\",\"doi\":\"10.1002/ardp.70078\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n <p>Seven new quinoline derivatives with different functional groups at positions 2, 3, and 4 were synthesized and subsequently assessed for their biological activities. Four synthesized compounds exhibited significant cytotoxic effects against A549 and MCF7 cells. Compound <b>4f</b> demonstrated IC<sub>50</sub> values comparable to that of the standard drug doxorubicin and showed a similar selectivity profile, exhibiting low toxicity toward healthy NIH3T3 cells. Furthermore, compound <b>4f</b> displayed a strong EGFR inhibition profile with an IC<sub>50</sub> value of 0.015 ± 0.001 µM. Molecular docking studies revealed that <b>4f</b> forms strong interactions with key amino acids on the active site of EGFR. Additionally, DFT analyses were conducted to calculate dipole moments, HOMO-LUMO energy gaps, and molecular electrostatic potential maps. Theoretical and experimental NMR chemical shift values showed a high correlation and confirmed the consistency of the computational results. These results indicate the potential of quinoline derivatives, especially of compound <b>4f</b>, as promising candidates for the development of chemotherapeutic agents.</p></div>\",\"PeriodicalId\":128,\"journal\":{\"name\":\"Archiv der Pharmazie\",\"volume\":\"358 8\",\"pages\":\"\"},\"PeriodicalIF\":3.6000,\"publicationDate\":\"2025-08-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archiv der Pharmazie\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ardp.70078\",\"RegionNum\":3,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"CHEMISTRY, MEDICINAL\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archiv der Pharmazie","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ardp.70078","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Synthesis, Anticancer Evaluation, Molecular Docking, and DFT Studies of Substituted Quinoline Derivatives
Seven new quinoline derivatives with different functional groups at positions 2, 3, and 4 were synthesized and subsequently assessed for their biological activities. Four synthesized compounds exhibited significant cytotoxic effects against A549 and MCF7 cells. Compound 4f demonstrated IC50 values comparable to that of the standard drug doxorubicin and showed a similar selectivity profile, exhibiting low toxicity toward healthy NIH3T3 cells. Furthermore, compound 4f displayed a strong EGFR inhibition profile with an IC50 value of 0.015 ± 0.001 µM. Molecular docking studies revealed that 4f forms strong interactions with key amino acids on the active site of EGFR. Additionally, DFT analyses were conducted to calculate dipole moments, HOMO-LUMO energy gaps, and molecular electrostatic potential maps. Theoretical and experimental NMR chemical shift values showed a high correlation and confirmed the consistency of the computational results. These results indicate the potential of quinoline derivatives, especially of compound 4f, as promising candidates for the development of chemotherapeutic agents.
期刊介绍:
Archiv der Pharmazie - Chemistry in Life Sciences is an international journal devoted to research and development in all fields of pharmaceutical and medicinal chemistry. Emphasis is put on papers combining synthetic organic chemistry, structural biology, molecular modelling, bioorganic chemistry, natural products chemistry, biochemistry or analytical methods with pharmaceutical or medicinal aspects such as biological activity. The focus of this journal is put on original research papers, but other scientifically valuable contributions (e.g. reviews, minireviews, highlights, symposia contributions, discussions, and essays) are also welcome.