Ohnishi H, Yamaguchi K, Shimada S, Himuro S, Suzuki Y
Antimicrob Agents Chemother. 1982 Aug;22(2):250-4. doi: 10.1128/AAC.22.2.250.
Sodium 5-aminosulfonyl-2,4-dichlorobenzoate (M12325) was evaluated for antiviral activity in tissue culture and infected mice. At concentrations ranging from 2.5 to 75.8 micrograms/ml, M12325 inhibited the cytopathic effects of 10 mean tissue culture infective doses of influenza virus A/WSN, A/FM, A/Kumamoto, and B/Great Lakes; parainfluenza virus; rhinovirus; echovirus; respiratory syncytial virus; and vesicular stomatitis virus. Concentrations up to 150 micrograms/ml did not inhibit the cytopathic effects of herpes simplex virus, vaccinia virus, or adenovirus. Concentrations up to 3,160 micrograms/ml did not inhibit the growth of MDCK, Vero, or HEL cells in culture. Single oral doses of M12325, ranging from 10 to 300 mg/kg, administered 1 h before and 1 h after challenge, reduced mortality in mice inoculated intranasally with influenza A/WSN virus. Twice daily oral doses for 14 days effected significant reductions in the mortality of mice infected intranasally with influenza A/WSN, A/FM, A/Kumamoto, and B/Great Lakes, and parainfluenza virus, but they were not effective in mice infected with herpes simplex virus. Multiple doses of 10 and 30 mg/kg, administered intraperitoneally, reduced lung consolidation and virus titer. M12325 was well tolerated in multiple doses up to 1 g/kg orally. These observations support the conclusions that M12325 has a broad spectrum of activity against RNA viruses in vitro and in vivo, selective toxicity, and a large margin of safety.
对5-氨基磺酰基-2,4-二氯苯甲酸钠(M12325)进行了组织培养和感染小鼠体内的抗病毒活性评估。在浓度范围为2.5至75.8微克/毫升时,M12325可抑制10个平均组织培养感染剂量的甲型流感病毒A/WSN、A/FM、A/熊本及乙型流感病毒B/大湖株、副流感病毒、鼻病毒、埃可病毒、呼吸道合胞病毒和水疱性口炎病毒的细胞病变效应。浓度高达150微克/毫升时,M12325不会抑制单纯疱疹病毒、痘苗病毒或腺病毒的细胞病变效应。浓度高达3160微克/毫升时,M12325不会抑制培养中的MDCK、Vero或HEL细胞生长。在攻毒前1小时和攻毒后1小时给予单次口服剂量为10至300毫克/千克的M12325,可降低经鼻接种甲型流感病毒A/WSN的小鼠死亡率。每日口服两次,连续14天,可显著降低经鼻感染甲型流感病毒A/WSN、A/FM、A/熊本及乙型流感病毒B/大湖株和副流感病毒的小鼠死亡率,但对感染单纯疱疹病毒的小鼠无效。腹腔注射10毫克/千克和30毫克/千克的多次剂量可减轻肺部实变并降低病毒滴度。口服多剂量高达1克/千克时,M12325耐受性良好。这些观察结果支持以下结论:M12325在体外和体内对RNA病毒具有广谱活性、选择性毒性和较大的安全范围。