An investigation into the biological activity of the selected histidine-containing diketopiperazines cyclo(His-Phe) and cyclo(His-Tyr)
An investigation into the biological activity of the selected histidine-containing diketopiperazines cyclo(His-Phe) and cyclo(His-Tyr)
复制标题
DOI：
10.1211/0022357044139
复制
发表时间：
2004-09-01
影响因子：
3.3
通讯作者：
Dyason, K
中科院分区：
文献类型：
--
作者：
McCleland, K;Milne, PJ;Dyason, K
尽管自世纪开始就已知环状二酮哌嗪，但直到现在它们才因其生物活性而引起相当大的兴趣。本研究的目的是确定二酮哌嗪环（L-组氨酰-L-苯丙氨酰）（环（His-Phe））和环（L-组氨酰-L-酪氨酰）（环（His-Tyr））是否具有与治疗心血管相关疾病状态、癌症和感染性疾病相关的显著生物活性。进行血液学研究，包括凝血酶底物结合、凝血时间、血小板粘附、血小板聚集和纤维蛋白溶解测定。利用基于四唑的试验对细胞系HeLa、WHCO 3和MCF-7进行细胞毒性筛选。采用全细胞膜片钳技术研究了大鼠心室肌细胞离子通道的活动，并进行了离体大鼠心脏研究，以研究心率和冠状动脉流量对心脏的影响。Cyclo（His-Tyr）能显著延长血小板的凝血时间，减缓血栓溶解，抑制ADP诱导的血小板粘附和聚集（P
Although cyclic diketopiperazines have been known since the beginning of the century, only now have they attracted considerable interest with respect to their biological activity. The aim of this study was to determine if the diketopiperazines cyclo(L-histidyl-L-phenylalanyl) (cyclo(His-Phe)) and cyclo(L-histidyl-L-tyrosyl) (cyclo(His-Tyr)) have significant biological activity relevant to the treatment of cardiovascular-related disease states, cancer and infectious diseases. Haematological studies were performed, including thrombin substrate binding, blood clotting time, platelet adhesion, platelet aggregation and fibrinolysis assays. A cytotoxicity screening utilizing a tetrazolium-based assay on the cell lines HeLa, WHCO3, and MCF-7 was performed. The whole-cell patch-clamp technique was used to investigate ion-channel activity in ventricular myocytes of rats, and isolated rat heart studies were performed to investigate the cardiac effects involving heart rate and coronary flow rate. Cyclo(His-Tyr) produced a significant prolongation of blood clotting time, slowing of clot lysis and inhibition of ADP-induced platelet adhesion and aggregation (P