|
- 2016
18β-甘草次酸哌嗪衍生物抗肝癌SMMC-7721细胞活性研究
|
Abstract:
摘要:目的 研究18β-甘草次酸哌嗪衍生物D34、D35对SMMC-7721细胞增殖的的抑制作用及对凋亡的影响。方法 用18β-甘草次酸哌嗪衍生物D34、D35以不同浓度、不同时间段处理SMMC-7721细胞,显微镜下观察其对肝癌SMMC-7721细胞形态结构的影响;MTT法检测18β-甘草次酸哌嗪衍生物D34、D35对SMMC-7721细胞的增殖抑制率;Hoechst-33258细胞凋亡染色试剂盒检测细胞凋亡情况;Annexin V-FITC/PI双染法检测细胞凋亡率。结果 MTT检测结果表明,18β-甘草次酸哌嗪衍生物D34、D35能够抑制肝癌SMMC-7721细胞增殖,且呈浓度依赖性(P<0.05);流式细胞仪检测细胞凋亡率,D35为26.71%、D34为36.95%。结论 18β-甘草次酸哌嗪衍生物D34、D35对SMMC-7721细胞有增殖抑制作用和促凋亡作用,且优于18β-甘草次酸(GA)。
ABSTRACT: Objective To study the effects of 18β-glycyrrhetinic acid derivatives containing piperazine D34 and D35 on the proliferation and apoptosis of SMMC-7721cells. Methods The morphology of the cells treated with 18β-glycyrrhetinic acid derivatives containing piperazine D34 and D35 was observed under the microscope. The cellular inhibition rate was detected by MTT; apoptosis was detected by Hoechst-33258 Staining Kit; and apoptosis rate was analyzed by flow cytometry method. Results The proliferation of SMMC-7721 cells was significantly inhibited by 18β-glycyrrhetinic acid derivatives containing piperazine D34 and D35 in a dose-dependent manner (P<0.05). Conclusion 18β-glycyrrhetinic acid derivatives containing piperazine D34 and D35 can inhibit the proliferation and induce the apoptosis of SMMC-7721 cells, and they are superior to GA
[1] | 康蕾,李学强,王凤荣. 18β-甘草次酸结构修饰及生物活性研究进展[J]. 中草药, 2012, 43(7):1430-1442. |
[2] | 魏梦雪,马超,陈凑喜,等. 新型双氢青蒿素哌嗪―芳香酰胺类化合物的合成及其抗肿瘤活性的初步评价[J]. 化学通报, 2015, 78(12):1090-1095. |
[3] | HASAN SK, SIDDIQI A, NAFEES S, et al. Chemopreventive effect of 18β-glycyrrhetinic acid via modulation of inflammatory markers and induction of apoptosis in human hepatoma cell line (HepG2)[J]. Mol Cell Biochem, 2016, 416(1-2):169-177. |
[4] | 高振北,胡君,康潇,等. 18β-甘草次酸 A 环官能团化衍生物的合成及抗肿瘤活性[J]. 高等学校化学学报, 2012, 33(4):750-754. |
[5] | 尹素改,周凌,吴耀松,等. 甘草次酸对人食管癌Eca9706细胞生长的抑制作用及机制 [J].中国实验方剂学杂志 2015, 21(4):112-114. |
[6] | 张娜,崔晓燕,赵秀梅,等. 甘草次酸衍生物的合成及其抗肝癌活性[J]. 中国实验方剂学杂志, 2015, 21(19):37-41. |
[7] | RADWAN MO, ISMAIL MAH, EL-MEKKAWY S, et al. Synthesis and biological activity of new 18β-glycyrrhetinic acid derivatives[J]. Arabian J Chem, 2013, 9(3):390-399. |
[8] | 蔡佳利,卢一卉,甘淋玲,等. 含哌嗪类抗微生物药物研究进展[J]. 中国抗生素杂志, 2009, 34(8):454-462. |
[9] | HUANG L, ZHANG WJ, ZHANG XH, et al. Synthesis and pharmacological evaluation of piperidine (piperazine)-substituted benzoxazole derivatives as multi-target antipsychotics[J]. Bioorg Med Chem Lett, 2015, 25(22):5299-5305. |
[10] | ISHIDA T, MIKI I, TANAHASHI T, et al. Effect of 18β-glycyrrhetinic acid and hydroxypropyl γ cyclodextrin complex on indomethacin-induced small intestinal injury in mice[J]. Eur J Pharmacol, 2013, 714(1-3):125-131. |
[11] | CINATL J, MORGENSTERN B, BAUER G, et al. Glycyrrhizin, an active component of liquorice roots, and replication of SARS-associated coronavirus[J]. Lancet, 2003, 361(9374):2045-2046. |
[12] | KIM J, JOO I, KIM H, et al. 18β-Glycyrrhetinic acid induces immunological adjuvant activity of Th1 against Candida albicans surface mannan extract[J]. Phytomedicine, 2013, 20(11):951-955. |
[13] | JAYASOORIYA RGPT, DILSHARA MG, SANG RP, et al. 18β-Glycyrrhetinic acid suppresses TNF―a induced matrix metalloproteinase-9 and vascular endothelial growth factor by suppressing the Akt-dependent NF-kB pathway[J]. Toxicol Vitro, 2014, 28(5):751-758. |
[14] | 靳如芳,刘静,张金晓,等. 甘草次酸及其衍生物TY501对小鼠巨噬细胞RAW264.7 增殖的影响[J]. 药物评价研究, 2011, 34(4):255-257. |
[15] | PARIDA PK, SAU A, GHOSH T, et al. Synthesis and evaluation of triazole linked glycosylated 18β-glycyrrhetinic acid derivatives as anticancer agents[J]. Bioorg Med Chem Lett, 2014, 24(16):3865-3868. |
[16] | 覃瑶,王欣,李恒华,等. 甘草次酸衍生物的抗炎活性及水钠潴留作用的研究[J]. 华西药学杂志, 2013, 28(4):338-340. |