Abstract

A novel series of 3,5-disubstituted-1a,3,4-oxadiazole derivatives was synthesized and screened for in vitro anticancer activity. The newly synthesized compounds were characterized by ¹H, ¹³C NMR, IR spectroscopy and mass spectrometry. Among all the synthesized compounds, Oxaprozin derivatives containing 1,3,4-oxadiazole ring with 4-fluorobenzyl, 4-methoxybenzyl, methyl, and butyl substituents showed promising anticancer activity against HTB-57 cancer cell line, and derivatives with 4-fluorobenzyl, 4-methoxybenzyl, and propyl substituents exhibited a higher anticancer activity against a PPC-1 cell line. The possible binding mode interactions of the synthesized compounds with the key active site of the proline rich tyrosine kinase 2 Pyk2 receptor (PDB ID: 5TO8) were investigated using the AutoDock 4.2 docking protocol to find that the 1,3,4-oxadiazole Oxaprozin derivatives with methyl, ethyl, and propyl substituents had the highest binding energies (ΔG = –7.8, –7.6, and –6.8 kcal/mol, respectively) with Glu441, Leu431, Ala455, Val487, Met502, Leu556, Lys457, and Glu509.

中文翻译：

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新型1a，3,4-恶二唑衍生物作为细胞毒剂的设计与合成：结合实验和对接研究

摘要

合成了一系列新的3,5-二取代-1a，3,4-恶二唑衍生物，并筛选了其体外抗癌活性。新合成的化合物的特征在于¹ H，¹³13 C NMR，IR光谱和质谱。在所有合成的化合物中，含有带有4-氟苄基，4-甲氧基苄基，甲基和丁基取代基的1,3,4-恶二唑环的奥沙普嗪衍生物显示出对HTB-57癌细胞系的有希望的抗癌活性，以及​​带有4-氟苄基的衍生物， 4-甲氧基苄基和丙基取代基对PPC-1细胞系表现出更高的抗癌活性。使用AutoDock 4.2对接方案研究了合成的化合物与脯氨酸丰富的酪氨酸激酶2 Pyk2受体（PDB ID：5TO8）的关键活性位点之间可能的结合模式相互作用，以发现1,3,4-恶二唑奥沙普嗪衍生物带有甲基，乙基和丙基取代基的结合能最高（ΔG 分别为–7.8，–7.6和–6.8 kcal / mol），使用Glu441，Leu431，Ala455，Val487，Met502，Leu556，Lys457和Glu509。