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9-β-D-阿拉伯呋喃糖基腺嘌呤及其次黄嘌呤衍生物对1型单纯疱疹病毒的抑制浓度和致死浓度

Inhibitory and lethal concentrations of 9-beta-D-arabinofuranosyladenine and its hypoxanthine-derivative versus herpes simplex virus, type 1.

作者信息

Williams B B, Bailey E J, Lerner A M

出版信息

J Lab Clin Med. 1977 Apr;89(4):687-91.

PMID:191546
Abstract

Minimum inhibitory concentrations of 9-beta-D-arabinofuranosyladenine (ara-A, adenine arabinoside, vidarabine) and a purified preparation of 9-beta-D-arabinofuranosylhypoxanthine (arabinoslhypoxanthine, ara-Hx) at end points of 50% MIC50) and 100% (MIC100) reduction to challenges of approximately 50 p.f.u. of herpes simplex virus, type 1 (HSV-1) were determined in vero renal tissue cultures. Adenosine deaminase is universally present in tissue cultures and serum. These same tests were repeated in the presence of a potent inhibitor of adenosine deaminase, R-3-(2-deoxy-beta-D-erythro-pentofuranosyl)-3,6,7,8-tetrahydroimidazo-4,5-d)-(1,3)-diazepin-8-ol (co-vidarabine, co-ara-A). Addition of co-ara-A to assays of MIC50 or MIC100 for ara-A ensures standard reproducible results which can be compared in different laboratories. After incubations of HSV-1 in infected cultures for 96 hours, 35 degrees C., with concentrations of ara-A or ara-Hx at the MIC100 and over, cells were scraped and sonicated. Supernates were then reinoculated into vero flasks free of antiviral agents to determine minimum lethal concentrations (MLC's). Standard values (microng/ml.) for ara-A with co-ara-A are 11.3 (MIC50), 17.0 (MIC100), and 34.0 (MLC) but are 68.1 (MIC50), 170.4 (MIC100) and 375 (MLC) for ara-Hx. These data confirm that as a virustatic agent (MIC100) ara-A is 10 times more active than ara-Hx. Ara-A and ara-Hx have virucidal potentials which require approximately two times the respective MIC100.

摘要

在非洲绿猴肾细胞组织培养中,测定了9-β-D-阿拉伯呋喃糖基腺嘌呤(ara-A,阿糖腺苷,阿糖腺嘌呤)和纯化的9-β-D-阿拉伯呋喃糖基次黄嘌呤制剂(阿糖次黄嘌呤,ara-Hx)对大约50个空斑形成单位的1型单纯疱疹病毒(HSV-1)的50%(MIC50)和100%(MIC100)终点抑制浓度。腺苷脱氨酶普遍存在于组织培养物和血清中。在腺苷脱氨酶的强效抑制剂R-3-(2-脱氧-β-D-赤藓戊呋喃糖基)-3,6,7,8-四氢咪唑并[4,5-d]-[1,3]-二氮杂卓-8-醇(环磷腺苷,co-ara-A)存在的情况下重复了这些相同的试验。在ara-A的MIC50或MIC100测定中加入co-ara-A可确保获得可在不同实验室进行比较的标准可重复结果。在35℃下将HSV-1在感染的培养物中培养96小时,使用MIC100及以上浓度的ara-A或ara-Hx,然后刮下细胞并进行超声处理。然后将上清液重新接种到不含抗病毒剂的非洲绿猴肾细胞培养瓶中,以确定最小致死浓度(MLC)。ara-A与co-ara-A的标准值(微克/毫升)分别为11.3(MIC50)、17.0(MIC100)和34.0(MLC),而ara-Hx的标准值分别为68.1(MIC50)、170.4(MIC100)和375(MLC)。这些数据证实,作为一种病毒抑制剂(MIC100),ara-A的活性比ara-Hx高10倍。ara-A和ara-Hx具有杀病毒潜力,所需浓度约为各自MIC100的两倍。

相似文献

1
Inhibitory and lethal concentrations of 9-beta-D-arabinofuranosyladenine and its hypoxanthine-derivative versus herpes simplex virus, type 1.9-β-D-阿拉伯呋喃糖基腺嘌呤及其次黄嘌呤衍生物对1型单纯疱疹病毒的抑制浓度和致死浓度
J Lab Clin Med. 1977 Apr;89(4):687-91.
2
Antiherpesvirus activity in human sera and urines after administration of adenine arabinoside: in vitro and in vivo synergy of adenine arabinoside and arabinosylhypoxanthine in combination.阿糖腺苷给药后人体血清和尿液中的抗疱疹病毒活性:阿糖腺苷与阿糖次黄嘌呤联合应用的体内外协同作用。
J Clin Invest. 1978 Dec;62(6):1142-53. doi: 10.1172/JCI109233.
3
Deoxyadenosine antagonism of the antiviral activity of 9-beta-D-arabinofuranosyladenine and 9-beta-D-arabinofuranosylhypoxanthine.脱氧腺苷对9-β-D-阿拉伯呋喃糖基腺嘌呤和9-β-D-阿拉伯呋喃糖基次黄嘌呤抗病毒活性的拮抗作用。
Cancer Res. 1978 Jul;38(7):1916-21.
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Incorporation of 1-beta-D-arabinofuranosylcytosine into DNA from herpes simplex virus resistant to 9-beta-D-arabinofuranosyladenine.将1-β-D-阿拉伯呋喃糖基胞嘧啶掺入对9-β-D-阿拉伯呋喃糖基腺嘌呤耐药的单纯疱疹病毒的DNA中。
Cancer Res. 1984 Jan;44(1):69-73.
5
Two approaches that increase the activity of analogs of adenine nucleosides in animal cells.两种提高腺嘌呤核苷类似物在动物细胞中活性的方法。
Cancer Res. 1975 Jun;35(6):1547-54.
6
Metabolism of arabinosyladenine in herpes simplex virus-infected and uninfected cells. Correlation with inhibition of DNA synthesis and role in antiviral selectivity.单纯疱疹病毒感染和未感染细胞中阿糖腺苷的代谢。与DNA合成抑制的相关性及在抗病毒选择性中的作用。
Biochem Pharmacol. 1984 Aug 1;33(15):2431-8. doi: 10.1016/0006-2952(84)90715-9.
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Antiviral activity of arabinosyladenine and arabinosylhypoxanthine in herpes simplex virus-infected KB cells: selective inhibition of viral deoxyribonucleic acid synthesis in synchronized suspension cultures.阿糖腺苷和阿糖次黄嘌呤在单纯疱疹病毒感染的KB细胞中的抗病毒活性:在同步悬浮培养物中对病毒脱氧核糖核酸合成的选择性抑制
Antimicrob Agents Chemother. 1976 Jan;9(1):120-7. doi: 10.1128/AAC.9.1.120.
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Comparison of the actions of 9-beta-D-arabinofuranosyl-2-fluoroadenine and 9-beta-D-arabinofuranosyladenine on target enzymes from mouse tumor cells.9-β-D-阿拉伯呋喃糖基-2-氟腺嘌呤与9-β-D-阿拉伯呋喃糖基腺嘌呤对小鼠肿瘤细胞靶酶作用的比较。
Cancer Res. 1982 Jun;42(6):2260-4.
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Interaction of 9-beta-D-arabinofuranosyladenine, 9-beta-D-arabinofuranosyladenine 5'-monophosphate, and 9-beta-D-arabinofuranosyladenine 5'-triphosphate with S-adenosylhomocysteinase.9-β-D-阿拉伯呋喃糖基腺嘌呤、9-β-D-阿拉伯呋喃糖基腺嘌呤5'-单磷酸酯和9-β-D-阿拉伯呋喃糖基腺嘌呤5'-三磷酸酯与S-腺苷同型半胱氨酸酶的相互作用。
Cancer Res. 1981 Feb;41(2):673-8.
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Antiviral activity in the rabbit cornea of adenine arabinoside, Ara-A 5' monophosphate, and hypoxanthine arabinoside; and interactions with adenosine deaminase inhibitor.阿糖腺苷、阿糖腺苷5′单磷酸酯及阿糖次黄嘌呤在兔角膜中的抗病毒活性;以及与腺苷脱氨酶抑制剂的相互作用。
J Gen Virol. 1977 Jul;36(1):199-202. doi: 10.1099/0022-1317-36-1-199.

引用本文的文献

1
Comparison of the effects of arabinosyladenine, arabinosylhypoxanthine, and arabinosyladenine 5'-monophosphate against herpes simplex virus, varicella-zoster virus, and cytomegalovirus with their effects on cellular deoxyribonucleic acid synthesis.阿糖腺苷、阿糖次黄嘌呤和阿糖腺苷5'-单磷酸对单纯疱疹病毒、水痘-带状疱疹病毒和巨细胞病毒的作用及其对细胞脱氧核糖核酸合成的作用的比较。
Antimicrob Agents Chemother. 1981 Jan;19(1):170-8. doi: 10.1128/AAC.19.1.170.
2
Antiherpesvirus activity in human sera and urines after administration of adenine arabinoside: in vitro and in vivo synergy of adenine arabinoside and arabinosylhypoxanthine in combination.阿糖腺苷给药后人体血清和尿液中的抗疱疹病毒活性:阿糖腺苷与阿糖次黄嘌呤联合应用的体内外协同作用。
J Clin Invest. 1978 Dec;62(6):1142-53. doi: 10.1172/JCI109233.