Abstract

In search of the new anticancer agents, a series of novel new 5-aryl-3-((quinolin-8-ylsulfonyl)methyl)-1,2,4-oxadiazole derivatives were synthesized using 2-(quinolin-8-ylsulfonyl)acetonitrile and readily available aromatic carboxylic acids. The newly synthesized derivatives were evaluated for their in vitro anticancer activity against MCF-7, A-549, HeLa cell lines. 5-(4-fluorophenyl)-3-((quinolin-8-ylsulfonyl)methyl)-1,2,4-oxadiazole and 5-(3,5-dichlorophenyl)-3-((quinolin-8-ylsulfonyl)methyl)-1,2,4-oxadiazole shows significant activity against tested cancer cell lines with IC₅₀ values ranging from 4.13 ± 0.64 to 29.23 ± 1.01 μM as compared to standard erlotinib. The results of the inhibitory assay of most active compounds against the wild type tyrosine kinase EGFR, which is one of the enzymes expressed in the MCF-7 and A-549 cell lines revealed that both 5-(4-fluorophenyl)-3-((quinolin-8-ylsulfonyl)methyl)-1,2,4-oxadiazole, 5-(3,5-dichlorophenyl)-3-((quinolin-8-ylsulfonyl)methyl)-1,2,4-oxadiazole, and 5-(3,5-dinitrophenyl)-3-((quinolin-8-ylsulfonyl)methyl)-1,2,4-oxadiazole compounds had greater potency in inhibiting tyrosine kinase EGFR than the standard drug erlotinib. The in silico studies of most active compounds and erlotinib were also carried out on EGFR receptor and observed that all the compounds had appreciable binding energies. Finally, the in silico pharmacokinetic profile was predicted for potent compounds using SWISS/ADME and pkCSM, where, all the compounds followed Lipinski, Lipinski, Veber, Egan and Muegge rules without any deviation.

中文翻译：

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5-Aryl-3-((Quinolin-8-ylsulfonyl)methyl)-1,2,4-Oxadiazoles 的合成：靶向 EGFR 的抗癌药物和计算机研究

摘要

为了寻找新的抗癌剂，使用 2-(quinolin-8-ylsulfonyl) 合成了一系列新型 5-aryl-3-((quinolin-8-ylsulfonyl)methyl)-1,2,4-oxadiazole 衍生物乙腈和容易获得的芳香族羧酸。评估了新合成的衍生物对 MCF-7、A-549、HeLa 细胞系的体外抗癌活性。5-(4-氟苯基)-3-((喹啉-8-基磺酰基)甲基)-1,2,4-恶二唑和 5-(3,5-二氯苯基)-3-((喹啉-8-基磺酰基)甲基)-1,2,4-恶二唑对测试的癌细胞系具有显着活性，IC 为₅₀与标准厄洛替尼相比，值范围为 4.13 ± 0.64 至 29.23 ± 1.01 μM。大多数活性化合物对野生型酪氨酸激酶 EGFR 的抑制试验结果显示，5-(4-氟苯基)-3-( (喹啉-8-基磺酰基)甲基)-1,2,4-恶二唑、5-(3,5-二氯苯基)-3-((喹啉-8-基磺酰基)甲基)-1,2,4-恶二唑，以及与标准药物厄洛替尼相比，5-(3,5-二硝基苯基)-3-((喹啉-8-基磺酰基)甲基)-1,2,4-恶二唑化合物在抑制酪氨酸激酶 EGFR 方面具有更强的效力。大多数活性化合物和厄洛替尼的计算机模拟研究也在 EGFR 受体上进行，观察到所有化合物都具有可观的结合能。最后，