苯并噻唑功能化的金属螯合剂的合成及生物活性

Benzothiazole Functionalized Metal Chelators:Synthesis and Bioactivities

设计、合成了2种苯并噻唑功能化的金属螯合剂:N,N'-双(水杨醛)缩-2,2'-(3-(苯并[d]噻唑-2-基)-1,2-苯基)二氧乙基二胺L1和N,N'-双(水杨醛)缩-2,2'-(4-(苯并[d]噻唑-2-基)-1,2-苯基)二氧乙基二胺L2。并通过比浊度分析、BCA实验、HRP/Amplex Red实验以及MTT实验检测它们的生物活性。发现这2种螯合剂都能有效抑制金属离子(Zn^2+、Cu^2+)诱导的Aβ1~40的聚集,能大幅减少Cu-Aβ加合物产生H2O2的量,有效抑制Zn^2+、Cu^2+诱导Aβ聚集而产生的神经细胞毒性,并大幅提高细胞存活率。作为比较,对非苯并噻唑功能化但螯合部位相同的螯合剂做了相同的生物活性测试,但其生物活性明显比苯并噻唑功能化的金属螯合剂的低。

Two benzothiazole modified metal chelators(N,N'-bis(salicylaldehyde)-2,2'-(3-(benzo[d]-thiozol-2-yl)-1,2-phenylene-dioxyethyldiamine(L1),N,N'-bis(salicylaldehyde)-2,2'-(4-(benzo[d]thiozol-2-yl)-1,2-phenylene-dioxyethyldiamine(L2)were designed and synthesized.The biological activities of chelators were determined by Turbidity Assay,BCA Protein Assay,HRP/Amplex Red Assay and MTT Assay.The results show that these two chelators could effectively prevent aggregation of Aβ1~40 induced by metal ion(such as Zn^2+,Cu^2+),dramatically reduce the product of H2O2 which caused by Cu^2+-Aβspecies,and inhibit Aβaggregation mediated cytotoxicity on PC12 cells.The same assays were carried out for non-benzothiozole functionalized analogue.The non-specific chelator also has above bioactivities,however,its effect was far less than that of the benzothiozole functionalized varieties.