Design, synthesis, and antiproliferative investigation of novel quinazolinones incorporating 1,3,4-oxadiazole and 1,2,4-triazole thioether moieties

IF 1.4 4区 化学 Q4 CHEMISTRY, INORGANIC & NUCLEAR
Zijian Li , Yanle Men , Suhua Gao , Peipei Cui , Hongying Wang , Baoquan Chen
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引用次数: 0

Abstract

In the current study, a series of 1,3,4-oxadiazole and 1,2,4-triazole derivatives linked to quinazolinone were designed and synthesized by using Phase Transfer Catalysis. The structures of the synthesized compounds were confirmed by their IR, 1H NMR, 13C NMR, and HR-ESI-MS spectroscopic data, and their in vitro antiproliferative activities against A549, Hela, MCF-7 as well as L929 were detected by using CCK-8 assay. The results demonstrated that most of the compounds showed better growth inhibitory effect than 5-FU on A549, Hela, and MCF-7 cell lines. Especially, 2-(5-((3-bromophenyl)thio)-1,3,4-oxadiazole-2-yl)quinazolin-4(3H)-one (8o), 4-amino-5-((4-nitrophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9m) and 2-(4-amino-5-(o-tolylthio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9b) showed good antiproliferative activity against A549 cells with IC50 value of 3.46, 2.96, and 3.44 μM, respectively. 2-(4-Amino-5-((3,5-difluorophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9h) and 4-amino-5-((4-nitrophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9m) had obvious inhibitory effects on Hela cells with IC50 values of 1.76 and 3.91 μM, respectively. 2-(4-Amino-5-((2-chlorophenyl)thio)-4H-1,2,4-triazol-3-yl)quinazolin-4(3H)-one (9i) showed high inhibitory activity against MCF-7 cells with IC50 value of 2.72 μM. Meanwhile, all compounds showed lower cytotoxicity to L929 cells than positive control drug 5-FU. In development, according to the above preliminary observation, these novel quinazolinones incorporating 1,3,4-oxadiazole and 1,2,4-triazole thioether moieties could become potential molecular templates for searching new antitumor agents.

含有 1,3,4-oxadiazole 和 1,2,4-riazole 硫醚分子的新型喹唑啉酮的设计、合成和抗增殖研究
本研究采用相转移催化法设计并合成了一系列与喹唑啉酮相连的 1,3,4-恶二唑和 1,2,4-三唑衍生物。通过红外光谱、1H NMR、13C NMR 和 HR-ESI-MS 光谱数据确认了合成化合物的结构,并利用 CCK-8 试验检测了这些化合物对 A549、Hela、MCF-7 和 L929 的体外抗增殖活性。结果表明,大多数化合物对 A549、Hela 和 MCF-7 细胞株的生长抑制效果优于 5-FU。特别是 2-(5-((3-溴苯基)硫基)-1,3,4-恶二唑-2-基)喹唑啉-4(3H)-酮(8o)、4-氨基-5-((4-硝基苯基)硫基)-4H-1,2、4-氨基-5-((4-硝基苯基)硫基)-4H-1,2,4-三唑-3-基)喹唑啉-4(3H)-酮(9m)和 2-(4-氨基-5-(邻甲苯硫基)-4H-1,2,4-三唑-3-基)喹唑啉-4(3H)-酮(9b)对 A549 细胞显示出良好的抗增殖活性,IC50 值分别为 3.46、2.96 和 3.46、2.96 和 3.44 μM。2-(4-氨基-5-((3,5-二氟苯基)硫)-4H-1,2,4-三唑-3-基)喹唑啉-4(3H)-酮(9h)和 4-氨基-5-((4-硝基苯基)硫)-4H-1,2,4-三唑-3-基)喹唑啉-4(3H)-酮(9m)对 Hela 细胞有明显的抑制作用,IC50 值分别为 1.76 和 3.91 μM。2-(4-氨基-5-((2-氯苯基)硫)-4H-1,2,4-三唑-3-基)喹唑啉-4(3H)-酮(9i)对 MCF-7 细胞具有较高的抑制活性,IC50 值为 2.72 μM。同时,所有化合物对 L929 细胞的细胞毒性均低于阳性对照药物 5-FU。根据上述初步观察,这些含有 1,3,4-恶二唑和 1,2,4-三唑硫醚分子的新型喹唑啉酮类化合物有望成为寻找新抗肿瘤药物的潜在分子模板。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
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来源期刊
CiteScore
2.60
自引率
7.70%
发文量
103
审稿时长
2.1 months
期刊介绍: Phosphorus, Sulfur, and Silicon and the Related Elements is a monthly publication intended to disseminate current trends and novel methods to those working in the broad and interdisciplinary field of heteroatom chemistry.
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