Synthesis of N-subsituted-2-(trifluoromethyl)benzimidazoles as promising EGFR/VEGFR2 dual inhibition through molecular docking studies

IF 2.2 4区 化学 Q3 CHEMISTRY, MULTIDISCIPLINARY Journal of the Iranian Chemical Society Pub Date : 2024-10-16 DOI:10.1007/s13738-024-03094-8
Samir M. El Rayes, Ibrahim A. I. Ali, Walid Fathalla, Mohamed A. Ghanem, Afaf H. El-Sagheer, Mohamed S. Nafie
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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).

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通过分子对接研究合成有望抑制 EGFR/VEGFR2 的 N-取代-2-(三氟甲基)苯并咪唑类化合物
我们以氯乙酸乙酯烷基化为基础,设计了一系列 17 种新的 2-(三氟甲基)-1H-苯并咪唑。相应的酯经过皂化和酰肼溶解,分别得到相应的酸和酰肼。酰肼与芳香醛和异硫氰酸盐反应,分别得到相应的酰肼和硫代氨基脲。利用酰肼和酸衍生物连接胺;通过 "DCC 和叠氮偶联 "方法连接伯胺和仲胺,最终得到一系列具有广泛亲油和亲水特性的 N-烷基-2-(2-(三氟甲基)-1H-苯并咪唑-1-基)乙酰胺。采用 MTT 法测试了活性最强的化合物对 MCF-7 细胞的细胞毒性。有些化合物对两种蛋白质具有活性,与共晶体配体(如化合物 7d)的关键氨基酸相互作用。与多柔比星(IC50 = 2.12 μM)相比,化合物 7d 的 IC50 值为 0.51 μM,具有很强的细胞毒性。
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来源期刊
CiteScore
4.40
自引率
8.30%
发文量
230
审稿时长
5.6 months
期刊介绍: JICS is an international journal covering general fields of chemistry. JICS welcomes high quality original papers in English dealing with experimental, theoretical and applied research related to all branches of chemistry. These include the fields of analytical, inorganic, organic and physical chemistry as well as the chemical biology area. Review articles discussing specific areas of chemistry of current chemical or biological importance are also published. JICS ensures visibility of your research results to a worldwide audience in science. You are kindly invited to submit your manuscript to the Editor-in-Chief or Regional Editor. All contributions in the form of original papers or short communications will be peer reviewed and published free of charge after acceptance.
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