Imidazole derivatives display extensive applications in pharmaceutical chemistry and have been investigated as bioactive compounds for medicinal chemistry. In this study, besides the starting materials (3a–c and 4a–c), synthesis, characterization, and biological activity studies were conducted on a total of 18 compounds, nine of which are known and the other nine are original. The compounds investigated in the study are a series of alkyl (7–15) and aryl (16–24) ether derivatives bearing substituted phenyl and imidazole rings, which were characterized using various methods including ¹H NMR, ¹³C NMR, FT-IR analysis, elemental analysis, and mass spectroscopy. Computer-aided drug design studies have been carried out to predict the biological activities of compounds. Besides DFT calculations, the binding affinities of the compounds to EGFR, VEGFR2, FGFR1, HSP90, hCA I, and hCA II were investigated. Additionally, drug-likeness and ADME analyses were performed on the compounds. Anticancer, antioxidant, and enzyme inhibition activity tests were performed in biological activity studies on the synthesized compounds. Among the synthesized compounds, compounds 17 and 19–24 generally exhibited inhibition profiles against the widespread cytosolic hCA I isozyme with IC₅₀ values ranging from 4.13 to 15.67 nM and cytosolic hCA II isozyme with IC₅₀ values ranging from 5.65 to 14.84 nM. L929 (mouse fibroblast cell line) was used as the control healthy cell line, and MCF7 (breast cancer), C6 (rat glioblastoma), and HT-29 (colon cancer) cells were used in cell culture studies as cancer cell lines. Before the study on cancer cells, all compounds were examined on healthy cells, and their cytotoxicity was determined. As a result of these data, studies continued with six compounds determined to be nontoxic. On cancerous cells, it was determined that compounds 3a, 3b, 4a, 4b, 4c, and 7 had cytotoxic effects on both colon cancer and brain tumors. It was found that compound 3b had a more toxic effect than cisplatin on the glioma cell line with an IC₅₀ value of 10.721 ± 0.38 μM, and compound 3a had a more toxic effect on the colon cancer cell line with an IC₅₀ value of 20.88 ± 1.02 μM. However, it was determined that the same compounds did not have a statistically significant effect on breast cancer. Flow cytometry studies also showed that when the IC₅₀ dose of compound 3b was applied to the C6 cell line, the cells tended to early and late apoptosis. Additionally, it has been shown by flow cytometry that the cell cycle stops in the G0/G1 phase. A similar effect was observed in the colon cancer cell line with compound 3a. Compound 3b caused early and late apoptosis of the colon cancer cell line with the applied IC₅₀ dose and stopped the cell cycle in the G0/G1 phase. Finally, the FRAP method studied all synthesized compounds’ antioxidant effects. According to the measured antioxidant power results, it was determined that no compound had a more effective reducing power than vitamin E.

中文翻译：

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咪唑衍生的烷基和芳基醚：合成、表征、体外抗癌和抗氧化活性、碳酸酐酶 I–II 抑制特性以及计算机模拟研究


咪唑衍生物在药物化学中显示出广泛的应用，并已作为药物化学的生物活性化合物进行了研究。在这项研究中，除了起始原料（3a-c和4a-c）外，还对总共18种化合物进行了合成、表征和生物活性研究，其中9种是已知的，另外9种是原始的。该研究中研究的化合物是一系列带有取代苯基和咪唑环的烷基（7-15）和芳基（16-24）醚衍生物，并使用各种方法进行了表征，包括 ¹ H NMR，< b1> C NMR、FT-IR 分析、元素分析和质谱。已经进行了计算机辅助药物设计研究来预测化合物的生物活性。除了DFT计算之外，还研究了化合物与EGFR、VEGFR2、FGFR1、HSP90、hCA I和hCA II的结合亲和力。此外，还对这些化合物进行了药物相似性和 ADME 分析。在对合成化合物的生物活性研究中进行了抗癌、抗氧化和酶抑制活性测试。在合成的化合物中，化合物 17 和 19-24 通常对广泛的胞质 hCA I 同工酶表现出抑制特性，IC ₅₀ 值范围为 4.13 至 15.67 nM，对胞质 hCA II 同工酶的 IC ₅₀ 值为10.721±0.38μM，化合物3a对结肠癌细胞系的毒性作用更强，IC ₅₀ 值为10.721±0.38μM。 IC ₅₀ 值为 20.88 ± 1.02 μM。然而，已确定相同的化合物对乳腺癌没有统计学上显着的影响。流式细胞术研究还表明，当IC ₅₀ 剂量的化合物3b应用于C6细胞系时，细胞倾向于早期和晚期凋亡。此外，流式细胞术显示细胞周期停止于G0/G1期。使用化合物3a在结肠癌细胞系中观察到类似的效果。化合物3b用IC ₅₀ 剂量引起结肠癌细胞系的早期和晚期凋亡，并使细胞周期停止在G0/G1期。最后，FRAP方法研究了所有合成化合物的抗氧化作用。根据测定的抗氧化能力结果，确定没有任何化合物比维生素 E 具有更有效的还原能力。