当前位置: X-MOL 学术Chem. Bio. Drug Des. › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Synthesis and evaluation of pyridinium‐hydrazone derivatives as potential antitumoral agents
Chemical Biology & Drug Design ( IF 3 ) Pub Date : 2018-03-13 , DOI: 10.1111/cbdd.13177
Sülünay Parlar 1 , Yalçın Erzurumlu 2 , Recep Ilhan 2 , Petek Ballar Kırmızıbayrak 2 , Vildan Alptüzün 1 , Ercin Erciyas 1
Affiliation  

The hydrazones of 4‐hydrazinylpyridinium bearing alkylphenyl groups on pyridinium nitrogen were synthesized and evaluated for their cytotoxic activity against MCF‐7, PC3, U2OS, and HEK293 cell lines by Wst1 cell proliferation assay. Cytotoxic activity results indicated that d derivatives having butylene chain; 4 and 5 series having naphthalene and anthracene ring systems showed high cytotoxic activity (IC50 = 3.27–8.54 μm) on cancer cells. 3d (4‐(2‐(4‐hydroxybenzylidene)hydrazinyl)‐1‐(4‐phenylbutyl)pyridinium bromide) was the most cytotoxic compound with IC50 value of 3.27 μm against MCF‐7. The most active derivatives (1d, 2d, 3d, 4, and 5 series) were selected to investigate for the effects on autophagy by analyzing the expression of autophagy marker proteins. The conversion of LC3‐I to its lipidated form LC3‐II is essential for autophagy and related to autophagosomes. According to our results, all tested compounds except for 3d induced lipidated form LC3‐II accumulation. Then, the effects of the compounds on p62 protein level were also analyzed by the immunoblotting as the autophagy inhibition results in accumulation of p62. Further molecular mechanistic studies including morphological analysis and live–death assays indicated that all tested compounds (1d, 2d, 3d, 4, and 5 series) are potent antitumoral molecules and all except for 3d have potential to inhibit autophagic flux.

中文翻译:

吡啶hydrhydr衍生物作为潜在抗肿瘤药的合成与评价

合成了吡啶氮上带有烷基苯基的4-肼基吡啶鎓的,并通过Wst1细胞增殖试验评估了它们对MCF-7,PC3,U2OS和HEK293细胞系的细胞毒活性。细胞毒活性结果表明,d衍生物具有丁烯链;45系列具有萘和蒽环体系表现出较高的细胞毒性活性(IC 50  = 3.27-8.54μ上癌细胞)。三维(4-(2-(4-羟基亚苄基)肼基)-1-(4-苯基丁基)溴化吡啶鎓)与IC最细胞毒性化合物50的3.27μ值针对MCF-7。最活跃的衍生产品(选择1d2d3d45系列)以通过分析自噬标记蛋白的表达来研究对自噬的影响。LC3-I向脂质形式LC3-II的转化对于自噬至关重要,并且与自噬体有关。根据我们的结果,除3d诱导的脂质化形式的LC3-II积累外,所有测试的化合物。然后,还通过免疫印迹分析了化合物对p62蛋白水平的影响,因为自噬抑制导致p62的积累。进一步的分子力学研究(包括形态分析和活死分析)表明,所有测试的化合物(1d2d3d45系列)是有效的抗肿瘤分子,除3d之外的所有分子均具有抑制自噬通量的潜能。
更新日期:2018-03-13
down
wechat
bug