期刊文献+
任意字段
题名或关键词
题名
关键词
文摘
作者
第一作者
机构
刊名
分类号
参考文献
作者简介
基金资助
栏目信息

甲硝唑衍生物混配配合物^(99m)TcN(PNP5)(MN-cys-OS)的制备及生物性能研究

SYNTHESIS AND EVALUATION OF BIOLOGICAL ACTIVITY OF A NOVEL ASYMMETRIC METRONDAZOLE DERIVATIVE ^(99m)TcN(PNP5)(MN-cys-OS)
下载PDF
导出
摘要 合成了一种新的含甲硝唑药效团的双功能配体:2-[3-(2-甲基-5-硝基咪唑基)丙酰胺基]-3-巯基丙酸(MN-cys-OS),并与[99mTcN]i2nt+中间体反应,制备得到一种99mTcN核标记的混配配合物:99mTcN(PNP5)(MN-cys-OS),其标记率大于95%.研究表明99mTcN(PNP5)(MN-cys-OS)为电中性、脂溶性配合物(P=3.17±0.06),具有较好的体外稳定性.正常昆明小鼠体内生物分布研究结果显示该配合物具有很快的肝、血清除性能,进一步的荷MA891肿瘤小鼠研究显示其具有一定的乏氧选择性,但肿瘤摄取较低. A novel metronidazole derivative, 2-E 3-（2-methyl-5-nitro-lH-imidazolyl） sulfhydry-propionic acid （MN-cys-OS）, was synthesized as a pharmacophore-containing propionylamino 1-3 bifunctional ligand. The corresponding asymmetrical ^99mTc nitrodo complex, 99mTcN （PNPS） （MN-cys-OS）, a potential tumor hypoxia marker, was prepared in high yield （〉95%） through [^99mTcN]int^2＋ precursor. ^99mTcN（PNPS）（MN-cys- OS） was found to be lipophilic （P=3.17±0. 06） and electroneutral, with good stability. The complex had fast clearance from liver and blood in normal Kunming mice, but displayed specific accumulation in hypoxic foci, with a low tumor uptake in MA 891 tumor-bearing mice.
作者 陆洁 孔德靖 陈振民 许明炎 王学斌
机构地区 放射性药物教育部重点实验室 北京师范大学化学学院
出处 《北京师范大学学报（自然科学版）》 CAS CSCD 北大核心 2008年第5期498-502,共5页 Journal of Beijing Normal University(Natural Science)
基金 放射性药物教育部重点实验室开放基金资助项目
关键词 ^99mTcN核配合物 肿瘤乏氧 2-[3-(2-甲基5硝基咪唑基)丙酰胺基]3-巯基丙酸 生物分布 ^99mTc-nitrodo complex tumor hypoxia 2-[-3-（2 methyl-5-nitro-lH-imidazolyl）-propionylamino]-3-sulfhydry-propionic acid biodistribution
分类号 TQ463.53 [化学工程—制药化工] O614.121 [理学—无机化学]
  • 相关文献

参考文献18

  • 1李桂圆.肿瘤乏氧化及其治疗策略[J].医学研究生学报,2003,16(1):56-58. 被引量：4
  • 2Bos R, Zhong H,Hanrahan C F,et al. Levels of hypoxiainducible factor-1 alpha during breast carcinogenesis[J]. J Natl Cancer Inst, 2001, 93:309
  • 3Koumenis C, Alarcon R, Hammond E, et al. Regulation of p53 by hypoxia dissociation of transcriptional repression and apoptosis from p53-dependent transactivation [J].Mol cell Bio, 2001,21:1297
  • 4Linder K E, Chan Y W, Cyr J E, et al. TcO(PnAO-1 (2 nitroimidazole)) [BMS-181321], a new technetium- containing nitroimidazole complex for imaging hypoxia: synthesis, characterization, and xanthine oxidse-catalyzed reduction [J]. J Med Chem, 1994, 37:9
  • 5陈跃,莫廷树,匡安仁,范成中,郑时龙,何玲,李举联.乏氧组织显像剂^(99)Tc^m-DTPA-甲硝唑的制备和荷瘤动物实验研究[J].中华核医学杂志,2000,20(2):78-81. 被引量：8
  • 6Melo T, Duncan J, Ballinger J R, et al. BRU59-21, a second-generation ^99m Tc-labeled 2-nitroimidazole for imaging hypoxia in tumors[J]. J Nucl Med, 2000, 41: 169
  • 7Das T, Banerjee S, Samuel G, et al. ^99mTc-labeling studies of a modified metronidazole and its biodistribution in tumor bearing animal models [J].Nuel Med Biol, 2003, 30:127
  • 8Chu Taiwei, Li Rujun, Hu Shaowen, et al. Preparation and biodistribution of technetium-99m -labeled 1-( 2- nitroimidazole- 1-yl)-propanhydroxyiminoamide (N2IPA) as a tumor hypoxia marker[J]. Nucl Med Biol, 2004, 31:199
  • 9Chu Taiwei, Hu Shaowen, Wei Bing, et al. Synthesis and biological results of the technetium-99m- labeled 4- nitroimindazole for imaging tumor hypoxia[J]. Bioorg Med Chem Lett, 2004,14:747
  • 10Mallia M B, Mathur A, Subramanian S, et al. A novel [^99m TcN]^2+ complex of metronidazole xanthate as a potential agent for targeting hypoxia[J].Bloorg Med Chem Lett, 2005, 15:3398

二级参考文献32

  • 1楚进锋,李彬,孔德靖,王学斌,张俊波,王金城,米宏志,赵建冬.[^(99)mTcN(PNP5)(NOEt)]^+新型心肌灌注显像剂研究[J].高等学校化学学报,2005,26(6):1014-1017. 被引量：7
  • 2楚进锋,李彬,孔德靖,王学斌,张俊波.新型^(99m)TcN核混配配合物的制备和小鼠生物分布[J].北京师范大学学报（自然科学版）,2006,42(5):514-517. 被引量：3
  • 3Mannan R H，J Nucl Med，1991年，32卷，1764页
  • 4Bos R, Zhong H, Hanrahan GF, et al. Level of hypoxia-induciblefactor-1 alpha during breast carcinogenesis[J]. Cancer Inst,2001,93(4):309-314.
  • 5Koumenis C,Alsrcon R, Hammond E, et al.Regulation of p53 by hypoxia dissociation of transcriptional repression and apoptosis from p53-dependent transactivition [J]. Mol Cell Biol, 2001,21(4):1297-1310.
  • 6Hockel M, Schlenger K, Mitze M, et al. Hypoxia and radiation response in human tumors[J]. Semin Radiat Oncol, 1996,6(1):3-9.
  • 7Sutherland RM, Ausserer WA, Murphy BJ, et al. Tumor hypixia and heterogeneity: challenges and opportunities for the future[J]. Semin Radiat Oncol, 1996,6(1):59-70.
  • 8Thrash Bingham CA,Tartof KD. AHIF: a natural antisense transcript overtxpressed in human renal cancer and during hypoxia[J]. J Natl Cancer Inst, 1999,91(2):143-151.
  • 9Zhong H, DeMarzo AM, Laughner E,et al.Overexpression of hypoxia-inducible factor lalpha in common human cancers and their metastases[J]. Cancer Res, 1999,59(22):5830-5835.
  • 10Maxwell PH, Dachs GU, Gleadle JM, et al. Hypoxia-inducible factor-1 modu lates gene exoressionin solid tumors and influences both angiogenesis and tumor growth[J]. Proc Natl Acad Sci Usa,1997,94(6): 8104-8109.

共引文献9

北京师范大学学报（自然科学版）
2008年 第5期

相关作者

内容加载中请稍等...

相关机构

内容加载中请稍等...

相关主题

内容加载中请稍等...

浏览历史

内容加载中请稍等...
;
使用帮助 返回顶部