Ya Yang, Zhen Jia, Taigui Ma, Qinyang Yu, Lei Tang, Yong Li, Lingling Fan
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引用次数: 0
摘要
为了发现有效的抗血小板凝集药物，我们设计并合成了 38 种新型丁基酞-羟基肉桂酸杂化衍生物。在这些化合物中，3 o对AA诱导的体外血小板聚集具有最佳的抑制活性，对凝血酶诱导的血小板收缩、卡拉胶诱导的尾部血栓形成和氯化铁诱导的颈总动脉血栓形成的抑制作用也优于前体3-正丁基邻苯二甲酸盐（NBP）。对抗缺血性脑卒中活性的进一步研究表明，化合物 3 o 对缺血性/再灌注脑损伤具有显著的保护作用。PAMPA-BBB 渗透性和肝微粒体稳定性测试表明，化合物 3 o 可通过血脑屏障，并具有良好的代谢稳定性。这项研究为治疗和预防由血栓形成引起的脑血管疾病提供了一种新的候选化合物。
Design and Synthesis of Butylphthalide-Hydroxycinnamic Acid Hybrid Derivatives as Potential Antiplatelet Agents.
Thirty-eight novel butylphthalide-hydroxycinnamic acid hybrid derivatives were designed and synthesized to discover effective antiplatelet agglutination drugs. Among these compounds, 3 o gave the optimal inhibitory activity against AA-induced platelet aggregation in vitro and also exhibited better inhibition than the precursor 3-n-butylphthalide (NBP) against thrombin-induced platelet contraction, carrageenan-induced tail thrombosis, and FeCl3-induced common carotid artery thrombosis. Further investigations on the anti-ischemic stroke activity revealed that compound 3 o exhibited a remarkable protective effect against ischemic/reperfusion brain injury. The PAMPA-BBB permeability and liver microsomal stability tests indicated that compound 3 o could traverse the blood-brain barrier and possessed favorable metabolic stability. This research provides a new candidate compound for treating and preventing cerebrovascular diseases caused by thrombosis.
期刊介绍：
Chemistry & Biodiversity serves as a high-quality publishing forum covering a wide range of biorelevant topics for a truly international audience. This journal publishes both field-specific and interdisciplinary contributions on all aspects of biologically relevant chemistry research in the form of full-length original papers, short communications, invited reviews, and commentaries. It covers all research fields straddling the border between the chemical and biological sciences, with the ultimate goal of broadening our understanding of how nature works at a molecular level.
Since 2017, Chemistry & Biodiversity is published in an online-only format.
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