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首页> 外文期刊>RSC Advances >Discovery of 4-(2-(dimethylamino)ethoxy)benzohydrazide derivatives as prospective microtubule affinity regulating kinase 4 inhibitors
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Discovery of 4-(2-(dimethylamino)ethoxy)benzohydrazide derivatives as prospective microtubule affinity regulating kinase 4 inhibitors

机译：发现4-（2-（二甲基氨基）乙氧基）苯肼衍生物作为前瞻性微管亲和力调节激酶4抑制剂

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Microtubule affinity regulating kinase 4 (MARK4) is a Ser/Thr kinase, considered as a potential drug target for cancer, diabetes and neurodegenerative diseases. Due to its significant role in the development and progression of cancer, different in-house libraries of synthesized small molecules were screened to identify potential MARK4 inhibitors. A small library of hydrazone compounds showed a considerable binding affinity to MARK4. The selected compounds were further scrutinized using an enzyme inhibition assay and finally two hydrazone derivatives ( H4 and H19 ) were selected that show excellent inhibition (nM range). These compounds have a strong binding affinity for MARK4 and moderate binding with human serum albumin. Anticancer studies were performed on MCF-7 and A549 cells, suggesting H4 and H19 selectively inhibit the growth of cancer cells. The IC _(50) value of compound H4 and H19 was found to be 27.39 μM and 34.37 μM for MCF-7 cells, while for A549 cells it was 45.24 μM and 61.50 μM, respectively. These compounds inhibited the colonogenic potential of cancer cells and induced apoptosis. Overall findings reflect that hydrazones/hydrazone derivatives could be exploited as potential lead molecules for developing effective anticancer therapies via targeting MARK4.
机译：微管亲和力调节激酶4（Mark4）是Ser / Thr激酶，被认为是癌症，糖尿病和神经变性疾病的潜在药物靶标。由于其在癌症的开发和进展中的显着作用，筛选了不同的合成小分子的内部内部文库以鉴定潜在的Mark4抑制剂。一小文库的腙化合物对MARK4显示了相当大的结合亲和力。使用酶抑制测定进一步仔细仔细仔细仔细仔细仔细仔细仔细仔细仔细仔细仔细仔细仔细仔细筛选，所述含有两种腙衍生物（H4和H19），其显示出优异的抑制（NM范围）。这些化合物对Mark4具有强的结合亲和力，与人血清白蛋白的中度结合。对MCF-7和A549细胞进行抗癌研究，表明H4和H19选择性地抑制癌细胞的生长。对于MCF-7细胞，发现化合物H4和H19的IC _（50）值为27.39μm和34.37μm，同时为A549细胞分别为45.24μm和61.50μm。这些化合物抑制了癌细胞的上衣潜力和诱导的细胞凋亡。总体发现反映了含腙/腙衍生物可以被利用为潜在的铅分子，用于通过靶向MARK4开发有效的抗癌疗法。

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