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新型人干细胞/祖细胞增殖激活剂:4-(4-(5-巯基-1,3,4-恶二唑-2-基)苯基)硫代氨基脲(司他唑)的合成及生物学评价

Synthesis and biological evaluation of a novel human stem/progenitor cells proliferation activator: 4-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl) thiosemicarbazide (Stemazole).

作者信息

Sun Ying, Wang Wei, Sun Yuanyuan, Han Mei

机构信息

Key Laboratory of Radiopharmaceuticals, Ministry of Education, College of Chemistry, Beijing Normal University, Beijing 100875, China.

出版信息

Eur J Med Chem. 2011 Jul;46(7):2930-6. doi: 10.1016/j.ejmech.2011.04.017. Epub 2011 Apr 12.

Abstract

Stem/progenitor cells are crucial for cell-based therapy and regenerative medicine, and their application in clinical and basic research requires a large supply of cells. To identify effective stem/progenitor cell proliferation activators, we synthesised a series of new 4-(4-(5-mercapto-1,3,4-oxadiazol-2-yl)phenyl) thiosemicarbazide (named Stemazole) derivatives. Preliminary evaluation of the structure-activity relationship (SAR) and the biological activities of the compounds were determined with a luminescent cell viability assay. The identified leading compound, Stemazole, exhibited remarkable proliferation-promoting activity in human hippocampal stem/progenitor cells (HSCs) in a time-dependent and concentration-dependent manner. The proliferation-promoting activity of Stemazole was further confirmed against a panel of human stem/progenitor cells derived from each of the three blastoderm layers. In conclusion, Stemazole is a novel activator of stem cells proliferation.

摘要

干/祖细胞对于基于细胞的治疗和再生医学至关重要,其在临床和基础研究中的应用需要大量的细胞。为了鉴定有效的干/祖细胞增殖激活剂,我们合成了一系列新的4-(4-(5-巯基-1,3,4-恶二唑-2-基)苯基)硫代氨基脲(命名为Stemazole)衍生物。通过发光细胞活力测定法对化合物的构效关系(SAR)和生物活性进行了初步评估。鉴定出的先导化合物Stemazole在人海马干/祖细胞(HSCs)中以时间依赖性和浓度依赖性方式表现出显著的增殖促进活性。Stemazole对源自三个胚层的一组人干/祖细胞的增殖促进活性得到了进一步证实。总之,Stemazole是一种新型的干细胞增殖激活剂。

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