Abstract：
The isatin group is widespread in nature and is considered to be a privileged building block for drug discovery. In order to develop novel SHP1 inhibitors with fluorescent properties as tools for SHP1 biology research, this work designed and synthesized a series of isatin derivatives. The presentive compound 5a showed good inhibitory activity against SHP1PTP with IC50 of 11 ± 3 μM, displayed about 92% inhibitory rate against MV-4-11 cell proliferation at the concentration of 20 μM, exhibited suitable fluorescent properties with a long emission wavelength and a large Stokes shift, and presented blue fluorescent imaging in HeLa cells with low cytotoxicity. This study could offer chemical tool to further understand SHP1 biology and develop novel SHP1 inhibitors in therapy.
摘要：
Isatin组广泛存在，被认为是药物发现的特权组成部分。为了开发具有荧光特性的新型SHP1抑制剂作为SHP1生物学研究的工具,本工作设计并合成了一系列的Isatin衍生物。化合物5a对SHP1PTP显示出良好的抑制活性,IC50为11±3μM,在20μM的浓度下，对MV-4-11细胞增殖的抑制率约为92％，具有长发射波长和大斯托克斯位移的合适荧光特性，并在低细胞毒性的HeLa细胞中呈现蓝色荧光成像。这项研究可以提供化学工具，以进一步了解SHP1生物学并开发治疗中的新型SHP1抑制剂。
