{"title":"通过连续 CuAAC 和 CH 芳基化合成喹啉融合 1,2,3 三唑衍生物;抗乳腺癌、抗EGFR 和 HER2 活性,计算研究","authors":"","doi":"10.1016/j.tetlet.2024.155282","DOIUrl":null,"url":null,"abstract":"<div><p>Some new quinoline linked fused 1,2,3-triazole hybrids (<strong>5a-5o</strong>) were synthesized <em>via</em> Cu(I) catalyzed azide-alkyne cycloaddition followed by intramolecular C<img>H arylation in one pot. Further, these derivatives were screened for their anti-breast cancer activity against MCF-7, MDA-MB-468 and MDA-MB-231 cell lines and results were compared with the 5-fluorouracil (5-FU). Out of all, compounds <strong>5a</strong>, <strong>5c</strong>, <strong>5f</strong>, <strong>5g</strong> and <strong>5j</strong> displayed higher activity than the 5-FU against three cancer cell lines. Compound <strong>5a</strong> was more effective in inhibiting both tyrosine kinase EGFR and HER2 enzymes than the Erlotinib and Lapatinib. Furthermore, compound <strong>5j</strong> demonstrated greater potency than the Erlotinib against EGFR. Molecular docking studies revealed the important binding features of most potent compounds <strong>5a</strong>, <strong>5c</strong>, <strong>5f</strong>, <strong>5g</strong> and <strong>5j</strong> with EGFR (PDB ID-4HJO) and HER2 (PDB ID-3RCD) and results were found to be supportive with corresponding IC<sub>50</sub> data. Finally, <em>in silico</em> pharmacokinetic studies revealed that compounds <strong>5a</strong>, <strong>5c</strong>, <strong>5f</strong>, <strong>5g</strong> and <strong>5j</strong> followed Ghose, Egan, Muegge, Lipinski and Veber rules without any deviation.</p></div>","PeriodicalId":438,"journal":{"name":"Tetrahedron Letters","volume":null,"pages":null},"PeriodicalIF":1.5000,"publicationDate":"2024-09-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Synthesis of quinoline fused 1,2,3-triazole derivatives via continuous CuAAC and CH arylation; anti-breast cancer, anti-EGFR and HER2 activities, computational studies\",\"authors\":\"\",\"doi\":\"10.1016/j.tetlet.2024.155282\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Some new quinoline linked fused 1,2,3-triazole hybrids (<strong>5a-5o</strong>) were synthesized <em>via</em> Cu(I) catalyzed azide-alkyne cycloaddition followed by intramolecular C<img>H arylation in one pot. Further, these derivatives were screened for their anti-breast cancer activity against MCF-7, MDA-MB-468 and MDA-MB-231 cell lines and results were compared with the 5-fluorouracil (5-FU). Out of all, compounds <strong>5a</strong>, <strong>5c</strong>, <strong>5f</strong>, <strong>5g</strong> and <strong>5j</strong> displayed higher activity than the 5-FU against three cancer cell lines. Compound <strong>5a</strong> was more effective in inhibiting both tyrosine kinase EGFR and HER2 enzymes than the Erlotinib and Lapatinib. Furthermore, compound <strong>5j</strong> demonstrated greater potency than the Erlotinib against EGFR. Molecular docking studies revealed the important binding features of most potent compounds <strong>5a</strong>, <strong>5c</strong>, <strong>5f</strong>, <strong>5g</strong> and <strong>5j</strong> with EGFR (PDB ID-4HJO) and HER2 (PDB ID-3RCD) and results were found to be supportive with corresponding IC<sub>50</sub> data. Finally, <em>in silico</em> pharmacokinetic studies revealed that compounds <strong>5a</strong>, <strong>5c</strong>, <strong>5f</strong>, <strong>5g</strong> and <strong>5j</strong> followed Ghose, Egan, Muegge, Lipinski and Veber rules without any deviation.</p></div>\",\"PeriodicalId\":438,\"journal\":{\"name\":\"Tetrahedron Letters\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":1.5000,\"publicationDate\":\"2024-09-10\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Tetrahedron Letters\",\"FirstCategoryId\":\"92\",\"ListUrlMain\":\"https://www.sciencedirect.com/science/article/pii/S0040403924003770\",\"RegionNum\":4,\"RegionCategory\":\"化学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"CHEMISTRY, ORGANIC\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Tetrahedron Letters","FirstCategoryId":"92","ListUrlMain":"https://www.sciencedirect.com/science/article/pii/S0040403924003770","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, ORGANIC","Score":null,"Total":0}
Synthesis of quinoline fused 1,2,3-triazole derivatives via continuous CuAAC and CH arylation; anti-breast cancer, anti-EGFR and HER2 activities, computational studies
Some new quinoline linked fused 1,2,3-triazole hybrids (5a-5o) were synthesized via Cu(I) catalyzed azide-alkyne cycloaddition followed by intramolecular CH arylation in one pot. Further, these derivatives were screened for their anti-breast cancer activity against MCF-7, MDA-MB-468 and MDA-MB-231 cell lines and results were compared with the 5-fluorouracil (5-FU). Out of all, compounds 5a, 5c, 5f, 5g and 5j displayed higher activity than the 5-FU against three cancer cell lines. Compound 5a was more effective in inhibiting both tyrosine kinase EGFR and HER2 enzymes than the Erlotinib and Lapatinib. Furthermore, compound 5j demonstrated greater potency than the Erlotinib against EGFR. Molecular docking studies revealed the important binding features of most potent compounds 5a, 5c, 5f, 5g and 5j with EGFR (PDB ID-4HJO) and HER2 (PDB ID-3RCD) and results were found to be supportive with corresponding IC50 data. Finally, in silico pharmacokinetic studies revealed that compounds 5a, 5c, 5f, 5g and 5j followed Ghose, Egan, Muegge, Lipinski and Veber rules without any deviation.
期刊介绍:
Tetrahedron Letters provides maximum dissemination of outstanding developments in organic chemistry. The journal is published weekly and covers developments in techniques, structures, methods and conclusions in experimental and theoretical organic chemistry. Rapid publication of timely and significant research results enables researchers from all over the world to transmit quickly their new contributions to large, international audiences.