氨基酸酯类化合物体外抗病毒活性的测定与评估  

Determination and evaluation of the antiviral activity of amino acid esters in vitro

作　　者：李妮 王海杰 胡康洪[1] 孙鸽[1] 魏艳红[1] LI Ni;WANG Hai-jie;HU Kang-hong;SUN Ge;WEI Yan-hong(Hubei Provincial Key Laboratory of Industrial Microbiology,Sino-German Biomedical Center,Hubei University of Technology,Wuhan 430068,China)

机构地区：[1]湖北工业大学湖北省工业微生物重点实验室,中德生物医学中心,湖北武汉430068

出　　处：《中国病原生物学杂志》2020年第7期789-794,共6页Journal of Pathogen Biology

基　　金：细胞调控与分子药物"111"引智基地青年学者国际合作研究基金资助项目(No.XBTK-2018005);湖北工业大学博士科研启动项目(No.BSQD2015004)。

摘　　要：目的探讨9种氨基酸酯化合物体外对柯萨奇病毒B组3型(CVB3)以及腺病毒7型(ADV-7)的抑制作用。方法根据细胞病变效应(CPE)观测结合噻唑蓝(MTT)比色法测定细胞存活率以确定化合物的抗病毒活性。计算化合物的半数中毒浓度(CC50)、半数有效浓度(IC50)和选择性治疗指数(SI)。采用CCID50法测定化合物对于子代病毒产量的抑制作用。结果9种氨基酸酯化合物对Hep-2和Hela细胞的毒性均较低,CC50均>100μg/ml。9种化合物对于CVB3均有一定的抑制作用,其中化合物3号(L-丙氨酸甲酯)和5号(β-丙氨酸乙酯)抗CVB3活性较强,最大抑制率分别为73.3%和74.3%,抑制活性与阳性对照化合物利巴韦林相当(最大抑制率为73.9%),治疗指数均>4。5号化合物对于CVB3的子代病毒产量表现出较强的抑制作用,相对于病毒对照组减少2.7 log。化合物2号(L-亮氨酸甲酯)和3号(L-丙氨酸甲酯)也表现出强的抗ADV-7活性,最大抑制率分别为65.0%和76.0%,治疗指数SI分别为5.1和6.3。结论9种氨基酸酯化合物均对CVB3和ADV-7病毒有抑制作用,且低毒高效,有潜力进一步开发为临床上使用的抗病毒药物。Objective To investigate the inhibitory effects of 9 amino acid esters on coxsackievirus group B type 3(CVB3)and adenovirus type 7(ADV-7)in vitro.Methods According to CPE observation and MTT colorimetry,the cell survival rate was determined to reflect the antiviral activity of compounds.The 50%cytotoxic concentration(CC50),50%inhibitory concentration(IC50)and selectivity index(SI)of 9 amino acid esters were calculated.The higher the SI value,the greater the antiviral potential of compounds.The CCID50 method was used to determine the inhibitory effect of compounds on the production of subsequent generations of the virus.Results The toxicity of 9 amino acid esters to Hep-2 and Hela cells was low,and CC50 was greater than 100 ug/mL.These compounds had certain inhibitory effects on CVB3.Compounds No.3(L-alanine methyl ester)and No.5(β-ethyl beta alanine)had more potent anti-CVB3 activity,with a maximum rate of inhibition of 73.3%and 74.3%,respectively,and an IC50 of 35.0μg/mL and 26.2μg/mL,respectively.Those compounds significantly inhibited the cytopathic effect of CVB3.The anti-CVB3 activity of Compound No.3 and No.5 was similar to that of ribavirin(maximum rate of inhibition:73.9%),and their selectivity index was greater than 4.Compound No.5 displayed a potent inhibitory effect on the production of CVB3 progeny,which was 2.7 log less than that of the virus control group.Compounds No.2(L-leucine methyl ester)and No.3(L-alanine methyl ester)also displayed potent anti-ADV-7 activity,with a maximum rate of inhibition of 65.0%and 76.0%,respectively,and an IC50 of 38.0μg/mL and 31.0μg/mL,respectively.Those compounds protected against the cytopathic effect of ADV-7,and they had a selectivity index of 5.1 and 6.3,respectively.Conclusion Nine amino acid esters inhibited CVB3 and ADV-7 with a low level of toxicity and high level of efficiency.They have the potential to be further developed into antivirals for clinical use.

关 键 词：氨基酸酯 柯萨奇病毒B组3型 腺病毒7型 

分 类 号：R373[医药卫生—病原生物学]