Samir M. El Rayes, Ibrahim A. I. Ali, Walid Fathalla, Mohamed A. Ghanem, Afaf H. El-Sagheer, Mohamed S. Nafie
{"title":"Synthesis of N-subsituted-2-(trifluoromethyl)benzimidazoles as promising EGFR/VEGFR2 dual inhibition through molecular docking studies","authors":"Samir M. El Rayes, Ibrahim A. I. Ali, Walid Fathalla, Mohamed A. Ghanem, Afaf H. El-Sagheer, Mohamed S. Nafie","doi":"10.1007/s13738-024-03094-8","DOIUrl":null,"url":null,"abstract":"<div><p>We have designed a series of 17 new 2-(trifluoromethyl)-1<i>H</i>-benzimidazoles based on alkylation with ethyl chloroacetate. The corresponding ester underwent saponification and hydrazinolysis to afford the corresponding acid and hydrazide, respectively. Hydrazide reacted with aromatic aldehydes and isothiocyanates and gave the corresponding hydrazones and thiosemicarbazide, respectively. The hydrazide and acid derivatives were used to attach an amine; primary and secondary amines via “DCC and azide coupling” methods to finally give a series of <i>N</i>-alkyl-2-(2-(trifluoromethyl)-1<i>H</i>-benzimidazol-1-yl)acetamides with a wide range of lipophilic and hydrophilic features. The most active compound was tested for cytotoxicity against MCF-7 cells using the MTT assay. Some compounds demonstrated activity against two proteins, interacting with key amino acids like the co-crystallized ligands such as compound 7d. Compound 7d exhibited potent cytotoxicity with an IC<sub>50</sub> value of 0.51 μM compared to Doxorubicin (IC<sub>50</sub> = 2.12 μM).</p></div>","PeriodicalId":676,"journal":{"name":"Journal of the Iranian Chemical Society","volume":"21 11","pages":"2743 - 2752"},"PeriodicalIF":2.2000,"publicationDate":"2024-10-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Journal of the Iranian Chemical Society","FirstCategoryId":"92","ListUrlMain":"https://link.springer.com/article/10.1007/s13738-024-03094-8","RegionNum":4,"RegionCategory":"化学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"CHEMISTRY, MULTIDISCIPLINARY","Score":null,"Total":0}
引用次数: 0
Abstract
We have designed a series of 17 new 2-(trifluoromethyl)-1H-benzimidazoles based on alkylation with ethyl chloroacetate. The corresponding ester underwent saponification and hydrazinolysis to afford the corresponding acid and hydrazide, respectively. Hydrazide reacted with aromatic aldehydes and isothiocyanates and gave the corresponding hydrazones and thiosemicarbazide, respectively. The hydrazide and acid derivatives were used to attach an amine; primary and secondary amines via “DCC and azide coupling” methods to finally give a series of N-alkyl-2-(2-(trifluoromethyl)-1H-benzimidazol-1-yl)acetamides with a wide range of lipophilic and hydrophilic features. The most active compound was tested for cytotoxicity against MCF-7 cells using the MTT assay. Some compounds demonstrated activity against two proteins, interacting with key amino acids like the co-crystallized ligands such as compound 7d. Compound 7d exhibited potent cytotoxicity with an IC50 value of 0.51 μM compared to Doxorubicin (IC50 = 2.12 μM).
期刊介绍:
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