在过去的十年里,涉及卤素键(HaB)作为主要相互作用的生物过程引起了极大的兴趣。然而,虽然结合碘原子被认为是强大的HaB供体,到目前为止,很少有碘化新药的报道。最近,碘化的4,4'-联吡啶在溶液和固态中作为HaB供体显示出有趣的特性。在本文中,描述了七种卤化4,4'-联吡啶对恶性黑色素瘤(MM)细胞增殖的抑制活性的研究。首先通过使用四种MM细胞系和正常BJ成纤维细胞细胞系作为对照,用三种4,4'-联吡啶进行探索性剂量/反应增殖测定。其中,A375MM细胞系最为敏感,通过MTT测定,选择它来评估所有4,4'-联吡啶的抗增殖活性。重要的是,亲电子碘的存在影响相应化合物的生物活性。3,3\',5,5'-四氯-2-碘-4,4'-联吡啶对A375细胞系显示出显着的抗增殖活性,对BJ成纤维细胞的毒性较低。通过计算机模拟研究,探索了决定生物活性的可能位点的立体电子特征。这些结果为利用碘化的4,4'-联吡啶作为模板设计新的有前途的HaB使能的MM细胞增殖抑制剂铺平了道路。
In the last decade, biological processes involving halogen bond (HaB) as a leading interaction attracted great interest. However, although bound iodine atoms are considered powerful HaB donors, few iodinated new drugs were reported so far. Recently, iodinated 4,4\'-bipyridines showed interesting properties as HaB donors in solution and in the solid state. In this paper, a study on the inhibition activity of seven halogenated 4,4\'-bipyridines against malignant melanoma (MM) cell proliferation is described. Explorative dose/response proliferation assays were first performed with three 4,4\'-bipyridines by using four MM cell lines and the normal BJ fibroblast cell line as control. Among them, the A375 MM cell line was the most sensitive, as determined by MTT assays, which was selected to evaluate the antiproliferative activity of all 4,4\'-bipyridines. Significantly, the presence of an electrophilic iodine impacted the biological activity of the corresponding compounds. The 3,3\',5,5\'-tetrachloro-2-iodo-4,4\'-bipyridine showed significant
antiproliferation activity against the A375 cell line, and lower toxicity on BJ fibroblasts. Through in silico studies, the stereoelectronic features of possible sites determining the bioactivity were explored. These results pave the way for the utilization of iodinated 4,4\'-bipyridines as templates to design new promising HaB-enabled inhibitors of MM cell proliferation.