Antiviral, antitumor, and thymidylate synthetase inhibition studies of 5-substituted styryl derivatives of 2'-deoxyuridine and their 5'-phosphates.
Antiviral, antitumor, and thymidylate synthetase inhibition studies of 5-substituted styryl derivatives of 2'-deoxyuridine and their 5'-phosphates.
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DOI：
10.1016/0006-2952(81)90635-3
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发表时间：
1981-03
影响因子：
5.8
通讯作者：
E. De Clercq;J. Balzarini;J. Descamps;C. Bigge;C. Chang;P. Kalaritis;M. Mertes
中科院分区：
文献类型：
--
作者：
E. De Clercq;J. Balzarini;J. Descamps;C. Bigge;C. Chang;P. Kalaritis;M. Mertes
本文研究了脱氧尿嘧啶核苷衍生物对痘苗病毒、单纯疱疹病毒复制(兔肾细胞原代培养)和小鼠白血病L-1210细胞生长的影响。5-苯乙基-2‘-脱氧尿苷对单纯疱疹病毒(1型和2型)诱导的细胞病变有50%的抑制作用，剂量为10~30μg/ml，对肿瘤细胞生长无抑制作用。相应的苯乙烯基衍生物对单纯疱疹病毒的ID50为30~70μg/ml，对痘苗病毒的ID50为20μg/ml，对L-12 10细胞生长的ID50为2 80μg/ml。5(E)-(3-叠氮苯乙基)-2‘-脱氧尿苷5’-磷酸对痘苗病毒复制的IC50为20μg/ml，对L-12 10细胞生长的ID50为80μg/ml，均为酪乳杆菌胸苷合成酶的可逆抑制物，其KIKm分别为：3-硝基-苯乙基，0.035.5%，4-硝基-苯乙基，0.0 6，0.0 8，0.31。研究了胸苷合成酶的光亲和标记试剂叠氮苯乙烯基衍生物在两个波长下的光解。
Deoxyuridine derivatives containing styryl, 3-nitrostyryl, 4-nitrostyryl, and phenylethyl groups substituted at the 5-position of the pyrimidine ring have been evaluated for their effects on vaccinia and herpes simplex virus replication (in primary rabbit kidney cell cultures) and mouse leukemia L-1210 cell culture growth. 5-Phenylethyl-2′-deoxyuridine inhibited herpes simplex (type 1 and 2) virus-induced cytopathogenicity by 50 per cent at a dose (id 50) of 10–30 μg/ml. It was inactive against tumor cell growth. The corresponding styryl derivative showed an id 50 of 30–70 μg/ml for herpes simplex virus, 20 μg/ml for vaccinia virus, and 280 μg/ml for L-1210 cell growth. 5 (E)-(3-Azidostyryl)-2′-deoxyuridine 5′-phosphate inhibited vaccinia replication with an IC 50 of 20 μg/ml and L-1210 cell culture growth with an id 50 of 80 μg/ml. The nucleotides of these compounds were all potent reversible inhibitors of thymidylate synthetase (Lactobacillus casei) with the following K i K m ratios: 3-nitrostyryl, 0.035; 4-nitrostyryl, 0.05; 3-azidostyryl, 0.06; styryl, 0.08; and phenylethyl, 0.31. The photodecomposition of the azidostyryl derivative, a photoaffinity labeling reagent for thymidylate synthetase, was examined at two wavelengths.