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二芳基胺类抗肿瘤先导物的结构修饰和活性评价

Synthesis and biological evaluation of diarylamines with antitumor activity
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摘要 对二芳基胺类抗肿瘤先导物1～3进行多位点结构修饰,设计合成了18个二芳基胺类衍生物,并在人肿瘤细胞系A549、DU145、KB和KB-vin上进行了抗肿瘤活性评价,发现化合物A6和B2具有较强的抑制肿瘤细胞生长活性(GI501.55～2.10μmol.L 1),化合物A9可选择性地抑制KB,KB-vin和DU145肿瘤细胞生长(GI501.10～2.00μmol.L 1)。获知的构效关系为进一步结构优化奠定了基础。 By structural modifications of our previous leads 1-3, 18 diarylamines were designed, synthesized and evaluated with a human tumor cell line panel, including A549, DU145, KB, and KB-vin cell lines, resulting in the discovery of new antitumor agents A6 and B2 with low micromolar GIs0 values ranging from 50 1.55-2.10μmol·L^-1 for above cell lines, and A9 with GI50 values ranging from 1.55-2.10μmol·L^-1 specially for DU145, KB, and KB-vin cells. Current structure-activity relationships are helpful for further lead optimization.
作者 王生彪 王晓锋 谢蓝
机构地区 中南大学药学院 军事医学科学院毒物药物研究所
出处 《药学学报》 CAS CSCD 北大核心 2013年第8期1273-1280,共8页 Acta Pharmaceutica Sinica
基金 国家自然科学基金资助项目(81120108022 30930106)
关键词 二芳基胺类衍生物 抗肿瘤活性 结构修饰 diarylamines antitumor activity lead optimization
分类号 R916 [医药卫生—药学]
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  • 1Lara PN Jr, Douillard JY, Nakagawa K, et al. Randomized phas m placebo-controlled trial of carboplatin and paclitaxel with 1 without the vascular disrupting agent vadimezan ( ASA404 ) i! advanced non-small-cell lung cancer [ J ]. J Clin Oncol, 2011[ 29(22) :2965-2971.
  • 2S~nchez-Pedregal VM, Griesinger C. The tubulin binding mode of MT stabilizing and destabilizing agents studied by NMR [ J ]. Top Curr Chem, 2009, 286 : 151-208.
  • 3Pettit GR, Kamano Y, Herald CL, et al. The isolation and struc- ture of a remarkable marine animal antineoplastic constituent : do- lastatin 10[J]. JAm Chem Soc, 1987, 109(22) :6883-6885.
  • 4Davis PD, Dougherty GJ, Blakey DC, et al. ZD6126: a novel vascular-targeting agent that causes selective destruction of tumor vasculature[ J]. Cancer Res, 2002, 62(24) :7247-7253.
  • 5Goto H, Yano S, Zhang H, et al. Activity of a new vascular tar- geting agent, ZD6126, in pulmonary metastases by human lung adenocarcinoma in nude mice [ J ]. Cancer Res, 2002, 62 ( 13 ) : 3711-3715.
  • 6Goto H, Yano S, Matsumori Y, et al. Sensitization of tumor-as- sociated endothelial cell apoptosis by the novel vascular-targeting agent ZD6126 in combination with cisplatin [ J ]. Clin Cancer Res, 2004, 10(22) :7671-7676.
  • 7Pettit GR, Cragg GM, Singh SB. Antineoplastic agents, 122. Constituents of Combretum caffrum [ J ]. J Nat Prod, 1987, 50 (3) :356-391.
  • 8Pettlt GR, Singh SB, Niven ML, et al. Isolation, structure, and synthesis of combretastatins A-1 and B-1, potent new inhibitors of microtubule assembly, derived from Combretum caffrum [ J ]. J Nat Prod, 1987, 50(1) :119-131.
  • 9Dowlati A, Robertson K, Cooney M, et al. A phase I phanna- eokinetic and translational study of the novel vascular targeting agent combretastatin a-4 phosphate on a single-dose intravenous schedule in patients with advanced cancer [ J ]. Cancer Res, 2002, 62(12) :3408-3416.
  • 10Kirwan IG, Loadman PM, Swaine D J, eta/. Comparative pre- clinical pharmacokinetic and metabolic studies of the combretasta- tin prodrugs combretastatin A4 phosphate and A1 phosphate[ J]. Clin Cancer Res, 2004, 10(4) :1446-1453.

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药学学报
2013年 第8期

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