设计并合成了新的芳香族 O-烷基吡啶衍生物作为前病毒整合莫洛尼 (PIM)-1 激酶抑制剂。 4c 和 4f 对 NFS-60、HepG-2、PC-3 和 Caco-2 细胞系显示出有效的体外抗癌活性，对正常人肺成纤维细胞 Wi-38 细胞系具有低毒性。此外，4c和4f在四种测试的癌细胞系中以高百分比诱导细胞凋亡。此外，4c和4f在HepG-2细胞系中显着诱导caspase 3/7激活。此外，4c 和 4f 显示出有效的 PIM-1 激酶抑制活性，IC50 分别为 0.110、0.095 µM。动力学研究表明4c和4f都是PIM-1激酶的竞争性和非竞争性抑制剂。此外，理化性质、药代动力学特征、配体效率、配体亲脂效率和诱导拟合对接研究的计算机预测与生物学和动力学研究一致，并预测4c和4f可以作为PIM-1激酶竞争性非-三磷酸腺苷 (ATP) 模拟物具有类似药物的特性。

New aromatic O-alkyl pyridine derivatives were designed and synthesised as Proviral Integration Moloney (PIM)-1 kinase inhibitors. 4c and 4f showed potent in vitro anticancer activity against NFS-60, HepG-2, PC-3, and Caco-2 cell lines and low toxicity against normal human lung fibroblast Wi-38 cell line. Moreover, 4c and 4f induced apoptosis in the four tested cancer cell lines with high percentage. In addition, 4c and 4f significantly induced caspase 3/7 activation in HepG-2 cell line. Furthermore, 4c and 4f showed potent PIM-1 kinase inhibitory activity with IC50 = 0.110, 0.095 µM, respectively. Kinetic studies indicated that 4c and 4f were both competitive and non-competitive inhibitors for PIM-1 kinase enzyme. In addition, in silico prediction of physiochemical properties, pharmacokinetic profile, ligand efficiency, ligand lipophilic efficiency, and induced fit docking studies were consistent with the biological and kinetic studies, and predicted that 4c and 4f could act as PIM-1 kinase competitive non-adenosine triphosphate (ATP) mimetics with drug like properties.