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林产化学与工业 ›› 2020, Vol. 40 ›› Issue (3): 123-129.doi: 10.3969/j.issn.0253-2417.2020.03.016

• 研究报告 • 上一篇    下一篇

三甲氧基没食子酸1, 2, 4-噻二唑-3, 5-二酮衍生物的合成及其对HL60细胞增殖的抑制作用

齐志文(),周昊,薛兴颖,颜洋洋,王成章*()   

  1. 中国林业科学研究院 林产化学工业研究所; 生物质化学利用国家工程实验室; 国家林业和草原局林产化学工程重点实验室; 江苏省生物质能源与材料重点实验室; 江苏省林业资源高效加工利用协同创新中心, 江苏 南京 210042
  • 收稿日期:2019-12-13 出版日期:2020-06-28 发布日期:2020-06-29
  • 通讯作者: 王成章 E-mail:115865567@qq.com;wangczlhs@sina.com
  • 作者简介:齐志文(1989-),男,湖北襄阳人,助理研究员,博士,从事林源活性物化学改性及活性研究; E-mail:115865567@qq.com
  • 基金资助:
    国家重点研发计划资助项目(2016YFD0600805);江苏省生物质能源与材料重点实验室基本科研业务费项目(JSBEM-201608)

Synthesis of 1, 2, 4-Thiadiazole-3, 5-dione Derivatives of Trimethoxy GallicAcid and Its Inhibition of HL60 Cell Line Proliferation

Zhiwen QI(),Hao ZHOU,Xingying XUE,Yangyang YAN,Chengzhang WANG*()   

  1. Institute of Chemical Industry of Forest Products, CAF; National Engineering Lab. for Biomass Chemical Utilization; Key Lab. of Chemical Engineering of Forest Products, National Forestry and Grassland Administration; Key Lab. of Biomass Energy and Material, Jiangsu Province; Jiangsu Co-Innovation Center of Efficient Processing and Utilization of Forest Resources, Nanjing 210042, China
  • Received:2019-12-13 Online:2020-06-28 Published:2020-06-29
  • Contact: Chengzhang WANG E-mail:115865567@qq.com;wangczlhs@sina.com

摘要:

合成了三甲氧基没食子酸1,2,4-噻二唑-3,5-二酮系列衍生物4a~4e,采用MTT法测定了中间产物23和目标化合物4a~4e对急性白血病HL60细胞增殖的抑制作用,并考察了4b4c与阳性对照TDZD-8对HL60细胞增殖抑制的协同作用。结果表明:化合物2~4对HL60细胞增殖均有一定的抑制作用,其中化合物4b4c抑制效果较好,半数抑制浓度(IC50)分别为10.60和6.31 μmol/L;而TDZD-8对HL60细胞的IC50值为0.30 μmol/L。此外,4b4c协同TDZD-8对急性白血病细胞株HL60具有较好的增殖抑制作用,当4b和TDZD-8浓度分别为5.0和0.34 μmol/L时,两者的协同抑制率为94.45%,协同指数CI值为0.58;当5c和TDZD-8浓度分别为5.0和0.34 μmol/L时,两者的协同抑制率为98.76%,协同指数(CI)值为0.31。可以看出,新型没食子酸1,2,4-噻二唑-3,5-二酮衍生物具有作为治疗人急性白血病药物先导物的潜力。

关键词: 没食子酸, 1, 2, 4-噻二唑-3, 5-二酮, TDZD-8, HL60, 协同作用

Abstract:

A series of 1, 2, 4-thiadiazole-3, 5-dione derivatives of trimethoxy gallic acid (4a-4e) were synthesized, and the intermediate products 2, 3 and the target compounds 4a-4e were tested against the proliferation of acute leukemia HL60 by MTT method.The inhibition of cell proliferation, and the synergistic effects of 4b and 4c and the positive control TDZD-8 on the proliferation inhibition of HL60 cells were investigated. The results showed that compounds 2-4 had a certain inhibitory effect on the proliferation of HL60 cells. Among them, compounds 4b and 4c had better inhibitory effects, and their half inhibitory concentrations (IC50) were 10.60 and 6.31 μmol/L, respectively and the IC50 value of TDZD-8 on HL60 cells was 0.30 mmol/L. In addition, 4b and 4c cooperated with TDZD-8 had better proliferation inhibitory effect on the acute leukemia cell line HL60. When the concentrations of 4b and TDZD-8 were 5.0 and 0.34 μmol/L, the synergistic inhibition rate of them was 94.45%, and the collaborative index(CI) value of the synergy index was 0.58; when the concentrations of 5c and TDZD-8 were 5.0 and 0.34 μmol/L, the synergistic inhibition rate was 98.76% and the CI value was 0.31. It could be seen that the new gallic acid 1, 2, 4-thiadiazole-3, 5-dione derivative could potentially act as the drug leader for treating human acute leukemia.

Key words: gallic acid, 1, 2, 4-thiadiazolidine-3, 5-dione, TDZD-8, HL60, synergistic

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