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学科主题: 药学
题名:
Synthesis of new class dipeptide analogues with improved permeability and antithrombotic activity
作者: Zhao, M; Bi, LR; Bi, W; Wang, C; Yang, Z; Ju, JF; Peng, SQ
关键词: dipeptide analogue ; antithrombotic activity ; membrane permeability
刊名: BIOORGANIC & MEDICINAL CHEMISTRY
发表日期: 2006-07-15
DOI: 10.1016/j.bmc.2006.03.026
卷: 14, 期:14, 页:4761-4774
收录类别: SCI
文章类型: Article
WOS标题词: Science & Technology
类目[WOS]: Biochemistry & Molecular Biology ; Chemistry, Medicinal ; Chemistry, Organic
研究领域[WOS]: Biochemistry & Molecular Biology ; Pharmacology & Pharmacy ; Chemistry
关键词[WOS]: NONCOVALENT THROMBIN INHIBITORS ; EPITHELIAL CACO-2 CELLS ; IN-VITRO PERMEABILITY ; PRO-ALA-LYS ; THROMBOLYTIC ACTIVITY ; INTESTINAL-ABSORPTION ; TRANSPORT MECHANISMS ; FIBRINOGEN FRAGMENT ; NITRONYL NITROXIDE ; DRUG TRANSPORT
英文摘要:

3-(S)-1,2,3,4-Tetrahydro-beta-carboline-3-carboxylic acid isolated from A. Chinese G. Don was found to possess moderate anti-aggregation activity, but with poor bioavailability. To improve its pharmacological property, we designed and synthesized a series of novel dipeptide analogues by incorporating tetrahydro-beta-carboline-3-carboxylic acid skeleton as an amino acid surrogate (*Trp). It turned out these dipeptide analogues exhibited good membrane permeability based on in vitro Caco-2 cell monolayers permeability assay. As a result, the overall biological properties of these molecules were significantly improved depending on the nature of the amino acid residues introduced onto the 3-position of the tetrahydro-beta-carboline moiety. It was very interesting to notice that these dipeptide analogues (5b,c,h,i,n,o,p,q) displayed a remarkable dual antiaggregatory activity in both of ADP- and PAF-induced platelet aggregation assay, and their aggregation response was significantly higher than that of aspirin (p < 0.01). In addition, these dipeptide analogues were observed for the dose-dependent antithrombotic effect using in vivo rat arterial thrombosis model. The potency of antithrombotic activity of 5h,i,n,p was significantly higher than that of aspirin (n = 12, p < 0.01) at equal dose (5 mu mol/kg). (c) 2006 Elsevier Ltd. All rights reserved.

语种: 英语
WOS记录号: WOS:000238698800008
Citation statistics:
内容类型: 期刊论文
URI标识: http://ir.bjmu.edu.cn/handle/400002259/61466
Appears in Collections:北京大学药学院_期刊论文

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作者单位: 1.USA Mitchell Canc Inst, Mobile, AL 36688 USA
2.Hebei Med Univ, Affiliated Hosp 2, Dept Surg, Shijiazhuang 050000, Peoples R China
3.Peking Univ, Coll Pharmaceut Sci, Beijing 100083, Peoples R China
4.Capital Univ Med Sci, Coll Pharmaceut Sci, Beijing 100054, Peoples R China

Recommended Citation:
Zhao, M,Bi, LR,Bi, W,et al. Synthesis of new class dipeptide analogues with improved permeability and antithrombotic activity[J]. BIOORGANIC &amp; MEDICINAL CHEMISTRY,2006,14(14):4761-4774.
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