NMR Laboratory, Institute of Chemical Sciences, Faculty of Science, P. J. Šafárik University in Košice, Moyzesova 11, 041 67 Košice, Slovakia.
Department of Biochemistry, Institute of Chemical Sciences, Faculty of Science, P. J. Šafárik University in Košice, Moyzesova 11, 041 67 Košice, Slovakia.
Molecules. 2022 Apr 30;27(9):2883. doi: 10.3390/molecules27092883.
A series of novel acridine N-acylhydrazone derivatives have been synthesized as potential topoisomerase I/II inhibitors, and their binding (calf thymus DNA—ctDNA and human serum albumin—HSA) and biological activities as potential anticancer agents on proliferation of A549 and CCD-18Co have been evaluated. The acridine-DNA complex 3b (-F) displayed the highest Kb value (Kb = 3.18 × 103 M−1). The HSA-derivatives interactions were studied by fluorescence quenching spectra. This method was used for the calculation of characteristic binding parameters. In the presence of warfarin, the binding constant values were found to decrease (KSV = 2.26 M−1, Kb = 2.54 M−1), suggesting that derivative 3a could bind to HSA at Sudlow site I. The effect of tested derivatives on metabolic activity of A549 cells evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide or MTT assay decreased as follows 3b(-F) > 3a(-H) > 3c(-Cl) > 3d(-Br). The derivatives 3c and 3d in vitro act as potential dual inhibitors of hTopo I and II with a partial effect on the metabolic activity of cancer cells A594. The acridine-benzohydrazides 3a and 3c reduced the clonogenic ability of A549 cells by 72% or 74%, respectively. The general results of the study suggest that the novel compounds show potential for future development as anticancer agents.
一系列新型吖啶 N-酰腙衍生物已被合成，作为潜在的拓扑异构酶 I/II 抑制剂，并对其与小牛胸腺 DNA（ctDNA）和人血清白蛋白（HSA）的结合（结合）以及作为潜在抗癌剂对 A549 和 CCD-18Co 增殖的生物活性进行了评估。吖啶-DNA 复合物 3b（-F）显示出最高的 Kb 值（Kb = 3.18 × 103 M−1）。通过荧光猝灭光谱研究了 HSA 衍生物的相互作用。该方法用于计算特征结合参数。在华法林存在下，发现结合常数值降低（KSV = 2.26 M−1，Kb = 2.54 M−1），表明衍生物 3a 可以在 Sudlow 位点 I 与 HSA 结合。通过 3-（4,5-二甲基噻唑-2-基）-2,5-二苯基四氮唑溴盐或 MTT 测定法评估测试衍生物对 A549 细胞代谢活性的影响如下：3b（-F）>3a（-H）>3c（-Cl）>3d（-Br）。衍生物 3c 和 3d 在体外对 hTopo I 和 II 具有潜在的双重抑制作用，对癌细胞 A594 的代谢活性具有部分作用。吖啶苯甲酰肼 3a 和 3c 分别使 A549 细胞的集落形成能力降低了 72%或 74%。研究的总体结果表明，这些新型化合物具有作为抗癌剂的未来发展潜力。
