Department of Organic Chemistry, Faculty of Chemical Engineering and Technology, University of Zagreb, Marulićev trg 19, HR-10000 Zagreb, Croatia.
Department of Biotechnology, University of Rijeka, Ulica Radmile Matejčić 2, HR-51000 Rijeka, Croatia.
Molecules. 2021 Nov 22;26(22):7060. doi: 10.3390/molecules26227060.
The novel 1,2,3-triazolyl-appended - and -heterocycles containing amidine - and amidoxime - moiety were prepared and evaluated for their antiproliferative activities in vitro. Among the series of amidine-substituted heterocycles, aromatic diamidine and coumarine amidine had the most potent growth-inhibitory effect on cervical carcinoma (HeLa), hepatocellular carcinoma (HepG2) and colorectal adenocarcinoma (SW620), with IC values in the nM range. Although compound was toxic to non-tumor HFF cells, compound showed certain selectivity. From the amidoxime series, quinoline amidoximes and showed antiproliferative effects on lung adenocarcinoma (A549), HeLa and SW620 cells emphasizing compound that exhibited no cytostatic effect on normal HFF fibroblasts. Results of CD titrations and thermal melting experiments indicated that compounds and most likely bind inside the minor groove of AT-DNA and intercalate into AU-RNA. Compounds , and bind to AT-DNA with mixed binding mode, most probably minor groove binding accompanied with aggregate binding along the DNA backbone.
新型 1,2,3-三唑基取代的含脒基和肟基部分的杂环被制备出来，并对其在体外的抗增殖活性进行了评估。在一系列的脒基取代的杂环中，芳香二脒 和香豆素脒 对宫颈癌（HeLa）、肝癌（HepG2）和结直肠腺癌（SW620）具有最强的生长抑制作用，IC 值在纳摩尔范围内。虽然化合物 对非肿瘤 HFF 细胞有毒性，但化合物 显示出一定的选择性。从肟基系列中，喹啉肟 和 对肺腺癌（A549）、HeLa 和 SW620 细胞具有增殖抑制作用，强调化合物 对正常 HFF 成纤维细胞没有细胞抑制作用。CD 滴定和热融实验的结果表明，化合物 和 很可能在 AT-DNA 的小沟内结合，并插入 AU-RNA。化合物 、 和 以混合结合模式与 AT-DNA 结合，最有可能是小沟结合，同时沿 DNA 主链聚集结合。
