Kodama E, Shigeta S, Suzuki T, De Clercq E
Department of Microbiology, Fukushima Medical College, Japan.
Antiviral Res. 1996 Jul;31(3):159-64. doi: 10.1016/0166-3542(96)06966-5.
We established a sensitive and accurate method for screening of anti-adenovirus agents using the 3-(4,5-dimetylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) method. MKN-28 cells, which are well-differentiated stomach adenocarcinoma cells, were used for adenovirus (ADV) infection and examined for the anti-ADV activities of several established anti-herpes virus agents. ADV-11 is the causative agent of respiratory and urinary infections. It frequently causes hemorrhagic cystitis in immunocompromised hosts. One laboratory strain and 4 clinical isolates of ADV-11 were examined, and found susceptible (in order of decreasing activity) to 2-amino-7-[(1,3-dihydroxy-2-propoxy)methyl]purine (S-2242), (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine[(S)-HPMPA ], and (S)-1-(3-hydroxy-2-phosphonylmethoxypropyl)cytosine[(S)-HPMPC++ +]. On the other hand, ganciclovir and iododeoxyuridine were only weakly effective and dextran sulfate was ineffective. Our findings indicate that the MTT assay using MKN-28 cells is applicable to anti-ADV screening. The anti-ADV activity of (S)-HPMPA and (S)-HPMPC was confirmed, and, furthermore, S-2242 emerged as a highly potent and selective inhibitor of ADV-11.
我们建立了一种灵敏且准确的方法,使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐(MTT)法筛选抗腺病毒药物。将高分化胃腺癌细胞MKN-28用于腺病毒(ADV)感染,并检测了几种已有的抗疱疹病毒药物的抗ADV活性。ADV-11是呼吸道和泌尿系统感染的病原体。它在免疫功能低下的宿主中常引起出血性膀胱炎。检测了1株ADV-11实验室菌株和4株临床分离株,发现它们对2-氨基-7-[(1,3-二羟基-2-丙氧基)甲基]嘌呤(S-2242)、(S)-9-(3-羟基-2-膦酰甲氧基丙基)腺嘌呤[(S)-HPMPA]和(S)-1-(3-羟基-2-膦酰甲氧基丙基)胞嘧啶[(S)-HPMPC++]敏感(活性依次降低)。另一方面,更昔洛韦和碘脱氧尿苷效果微弱,硫酸葡聚糖则无效。我们的研究结果表明,使用MKN-28细胞的MTT法适用于抗ADV筛选。(S)-HPMPA和(S)-HPMPC的抗ADV活性得到了证实,此外,S-2242是一种高效且选择性的ADV-11抑制剂。