鸢尾黄素衍生物的制备及抗其病毒活性研究

摘要：目的 通过对单体化合物鸢尾黄素的结构改造，寻找高效、低毒的新型抗病毒候选药物。方法 以鸢尾黄素为先导化合物合成了3个化合物，并以鸢尾黄素和利巴韦林为对照，考察化合物体外抗病毒的活性，观察的主要指标为半数毒性浓度(TC50)、半数抑制浓度(IC50)、抗病毒指数(TI)，为研发新抗病毒药物提供依据。结果 化学试验分别通过磺化反应合成化合物1，乙基化反应合成化合物2，乙基化、磺化反应两步合成化合物3，并根据红外、紫外、质谱和核磁等数据确定各化合物的结构，分别是鸢尾黄素-5'-磺酸钠、4',7-二乙基鸢尾黄素、4',7-二乙基鸢尾黄素-5'-磺酸钠；抗病毒研究表明各化合物组在不同剂量时对H3N2、ADV3、RSV、CVB3等病毒毒株均有不同程度的抑制作用，且明显强于同等剂量的鸢尾黄素组。化合物1对H3N2和RSV有明显的抑制作用，抗H3N2病毒指数为29.57，强于利巴韦林(15.87)；抗RSV病毒指数为28.39，略强于利巴韦林(27.29)；化合物2对CVB3有明显的抑制作用，抗CVB3病毒指数为31.60，略强于利巴韦林(29.00)；化合物3对H3N2和RSV有明显的抑制作用，抗RSV病毒指数为34.24，略强于利巴韦林(27.29)；抗H3N2病毒指数为35.56，远强于利巴韦林(15.87)。结论 化合物3具有高效、低毒的抗病毒活性，可作为潜在的抗H3N2病毒新药研发。

Research on the preparation and antiviral activity of the derivatives of tectorigenin

Abstract Objective To search for new antiviral drugs with high efficiency and low toxicity, through thestructural transformation of tectorigenin. Methods Three compounds were synthesized with tectorigenin as the leadcompound, and the antiviral activity of the compounds in vitro was investigated by comparing with tectorigenin andribavirin. The main indexes observed were TC50, IC50, and TI, which provided the basis for the development of newantiviral drugs. Results Chemical experiments were carried out to synthesize compound 1 by sulfonation reaction,compound 2 by ethylation reaction, and compound 3 by ethylation and sulfonation reaction. According to the data ofIR, UV, MS and NMR, the structures of the compounds were determined, which were tectorigenin-5'-sodium sulfonate,4',7-diethyl tectorigenin, and 4',7-diethyl tectorigenin-5'-sodium sulfonate. The antiviral study showed that eachcompound group inhibited H3N2, ADV3, RSV, and CVB 3 virus in different doses, and it was significantly strongerthan the same dose of tectorigenin group. Compound 1 had an obvious inhibitory effect on H3N2 and RSV, and its TIwas 29.57 for H3N2, stronger than ribavirin (15.87); its TI was 28.39 for RSV, slightly stronger than ribavirin (27.29).Compound 2 had an obvious inhibitory effect on CVB3, and its TI was 31.60, slightly stronger than ribavirin (29.00).Compound 3 had an obvious inhibitory effect on H3N2 and RSV, and its TI was 34.24 for RSV, slightly stronger thanribavirin (27.29); its TI was 35.56 for H3N2, much better than ribavirin (15.87). Conclusion Compound 3 had highantiviral activity and low toxicity. It can be used as a potential new drug against H3N2