Esraa Mahmoud, Dalia Abdelhamid, Bahaa G. M. Youssif, Hesham A. M. Gomaa, Alaa M. Hayallah, Mohamad Abdel-Aziz
{"title":"作为表皮生长因子受体和/或 c-MET 抑制剂的新型吲哚/1,2,4-三唑/查尔酮混合物的设计、合成和抗增殖活性","authors":"Esraa Mahmoud, Dalia Abdelhamid, Bahaa G. M. Youssif, Hesham A. M. Gomaa, Alaa M. Hayallah, Mohamad Abdel-Aziz","doi":"10.1002/ardp.202300562","DOIUrl":null,"url":null,"abstract":"<p>A novel group of indolyl-1,2,4-triazole-chalcone hybrids was designed, synthesized, and assessed for their anticancer activity. The synthesized compounds exhibited significant antiproliferative activity. Compounds <b>9a</b> and <b>9e</b> exhibited significant cancer inhibition with GI<sub>50</sub> ranging from 3.69 to 20.40 µM and from 0.29 to >100 µM, respectively. Both compounds displayed a broad spectrum of anticancer activity with selectivity ratios ranging between 0.50–2.78 and 0.25–2.81 at the GI<sub>50</sub> level, respectively. The synthesized compounds were also screened for their cytotoxicity by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazol (MTT) assay and for inhibition of epidermal growth factor receptor (EGFR) and c-MET (mesenchymal-epithelial transition factor). Some of the tested compounds exhibited significant inhibition against EGFR and/or c-MET. Compound <b>9b</b> showed the highest c-MET inhibition (IC<sub>50</sub> = 4.70 nM) compared to foretinib (IC<sub>50</sub> = 2.5 nM). Compound <b>9d</b> showed equipotent activity compared with erlotinib against EGFR (IC<sub>50</sub> = 0.052 µM) and displayed significant c-MET inhibition with an IC<sub>50</sub> value of 4.90 nM.</p>","PeriodicalId":128,"journal":{"name":"Archiv der Pharmazie","volume":null,"pages":null},"PeriodicalIF":4.3000,"publicationDate":"2024-06-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202300562","citationCount":"0","resultStr":"{\"title\":\"Design, synthesis, and antiproliferative activity of new indole/1,2,4-triazole/chalcone hybrids as EGFR and/or c-MET inhibitors\",\"authors\":\"Esraa Mahmoud, Dalia Abdelhamid, Bahaa G. M. Youssif, Hesham A. M. Gomaa, Alaa M. Hayallah, Mohamad Abdel-Aziz\",\"doi\":\"10.1002/ardp.202300562\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p>A novel group of indolyl-1,2,4-triazole-chalcone hybrids was designed, synthesized, and assessed for their anticancer activity. The synthesized compounds exhibited significant antiproliferative activity. Compounds <b>9a</b> and <b>9e</b> exhibited significant cancer inhibition with GI<sub>50</sub> ranging from 3.69 to 20.40 µM and from 0.29 to >100 µM, respectively. Both compounds displayed a broad spectrum of anticancer activity with selectivity ratios ranging between 0.50–2.78 and 0.25–2.81 at the GI<sub>50</sub> level, respectively. The synthesized compounds were also screened for their cytotoxicity by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazol (MTT) assay and for inhibition of epidermal growth factor receptor (EGFR) and c-MET (mesenchymal-epithelial transition factor). Some of the tested compounds exhibited significant inhibition against EGFR and/or c-MET. Compound <b>9b</b> showed the highest c-MET inhibition (IC<sub>50</sub> = 4.70 nM) compared to foretinib (IC<sub>50</sub> = 2.5 nM). Compound <b>9d</b> showed equipotent activity compared with erlotinib against EGFR (IC<sub>50</sub> = 0.052 µM) and displayed significant c-MET inhibition with an IC<sub>50</sub> value of 4.90 nM.</p>\",\"PeriodicalId\":128,\"journal\":{\"name\":\"Archiv der Pharmazie\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":4.3000,\"publicationDate\":\"2024-06-21\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ardp.202300562\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archiv der Pharmazie\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/ardp.202300562\",\"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.202300562","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"CHEMISTRY, MEDICINAL","Score":null,"Total":0}
Design, synthesis, and antiproliferative activity of new indole/1,2,4-triazole/chalcone hybrids as EGFR and/or c-MET inhibitors
A novel group of indolyl-1,2,4-triazole-chalcone hybrids was designed, synthesized, and assessed for their anticancer activity. The synthesized compounds exhibited significant antiproliferative activity. Compounds 9a and 9e exhibited significant cancer inhibition with GI50 ranging from 3.69 to 20.40 µM and from 0.29 to >100 µM, respectively. Both compounds displayed a broad spectrum of anticancer activity with selectivity ratios ranging between 0.50–2.78 and 0.25–2.81 at the GI50 level, respectively. The synthesized compounds were also screened for their cytotoxicity by 3-(4,5-dimethylthiazole-2-yl)-2,5-diphenyltetrazol (MTT) assay and for inhibition of epidermal growth factor receptor (EGFR) and c-MET (mesenchymal-epithelial transition factor). Some of the tested compounds exhibited significant inhibition against EGFR and/or c-MET. Compound 9b showed the highest c-MET inhibition (IC50 = 4.70 nM) compared to foretinib (IC50 = 2.5 nM). Compound 9d showed equipotent activity compared with erlotinib against EGFR (IC50 = 0.052 µM) and displayed significant c-MET inhibition with an IC50 value of 4.90 nM.
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.