新型神经氨酸酶抑制剂的设计合成和药理活性测试

Design, Synthesis and Pharmacological Activity Testing of the Novel Neuraminidase Inhibitor

关键词:  苯甲酸类  神经氨酸酶  流感病毒

Key words:  benzoic acid  neuraminidase  influenza virus

摘要:

目的 为防控流感，设计合成新型神经氨酸酶抑制剂，并进行药理活性测试。方法 基于苯甲酸类神经氨酸酶抑制剂的结构，拼合具有抗病毒活性的酰基硫脲片段，利用前药原理设计并合成了I和Ⅱ系列共28个新型神经氨酸酶抑制剂并进行药理活性筛选。药理活性测试选用流感病毒菌株A/FM/1/47（H1N1），分别进行神经氨酸酶单一浓度（10μmol·L^-1）抑制率和病毒抑制活性测试。结果 药理结果显示化合物I-2，I-5，I-11和I-12具有较好的病毒抑制活性，其中I-11的活性最佳，病毒抑制率达到70.50%，优于oseltamivir。结论 通过对28个化合物进行初步构效关系研究，为后续此类新型神经氨酸酶抑制剂的研究提供基础。

Abstract:

OBJECTIVE To design, synthesis novel neuraminidase inhibitors and detect their pharmacological activity for inhibite virus. METHODS The antiviral acyl thiourea fragments were integrated with the benzoic acid structure of neuraminidase inhibitors. Based on the pro-drug principle, 28 compounds were designed and synthesized and conduct the pharmacological activity screening. A/FM/1/47 (H1N1) strain was selected for the pharmacological activity test, and the single concentration(10 μmol·L^-1) inhibition rate of neuraminidase and in vitro virus inhibition test were performed respectively. RESULTS The results showed that I-2, I-5, I-11 and I-12 had desirable virus inhibitory activity, I-11 was the best among them. The virus inhibition rate of compound I-11 could reach 70.50%, which was superior to oseltamivir. CONCLUSION Preliminary study on structure-activity relationship of these 28 compounds will provide a basis for the design of the new neuraminidase inhibitors in the following study.