Nucleotide analogs related to acyclovir and ganciclovir are effective against murine cytomegalovirus infections in BALB/c and severe combined immunodeficient mice.
Nucleotide analogs related to acyclovir and ganciclovir are effective against murine cytomegalovirus infections in BALB/c and severe combined immunodeficient mice.
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与阿昔洛韦和更昔洛韦相关的核苷酸类似物可有效对抗 BALB/c 和严重联合免疫缺陷小鼠的鼠巨细胞病毒感染。
DOI：
10.1128/aac.38.9.2165
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发表时间：
1994
影响因子：
4.9
通讯作者：
Reist,EJ
中科院分区：
文献类型：
--
作者：
Smee,DF;Sugiyama,ST;Reist,EJ
评价了阿昔洛韦膦酸酯[9-（3-膦酰基-丙氧基甲基）鸟嘌呤; SR 3722]和更昔洛韦膦酸酯（9-[（（+/-）-1-羟甲基-3-膦酰基）丙氧基甲基]鸟嘌呤）的S对映体（SR 3772）、R对映体（SR 3773）和R，S对映体混合物（SR 3745 A）对小鼠巨细胞病毒的抗病毒活性。在感染鼠巨细胞病毒的严重联合免疫缺陷小鼠中，SR 3773和SR 3745 A（12.5、25和50 mg/kg体重/天）在延长平均死亡时间方面上级更昔洛韦，而SR 3722和SR 3772的效力低于更昔洛韦。在正常BALB/c小鼠中，SR 3773和更昔洛韦在预防死亡方面的活性大致相同。SR 3773以50 mg/kg/天剂量给药15天后引起肾小管损伤。这些结果表明，SR 3773可能用于治疗人巨细胞病毒感染，但也可能表现出肾毒性。
Acyclovir phosphonate [9-(3-phosphono-propyloxymethyl)guanine; SR3722] and the S enantiomer (SR3772), R enantiomer (SR3773), and R,S enantiomeric mixture (SR3745A) of ganciclovir phosphonate (9-[((+/-)-1-hydroxymethyl-3-phosphono)propyloxymethyl]guanine) were evaluated for their antiviral activities against murine cytomegalovirus. In severe combined immunodeficient mice infected with murine cytomegalovirus, SR3773 and SR3745A (12.5, 25, and 50 mg/kg of body weight per day) were superior to ganciclovir in extending the mean time to death, whereas SR3722 and SR3772 was less potent than ganciclovir. In normal BALB/c mice, SR3773 and ganciclovir were approximately equally active in preventing death. SR3773 caused renal tubular damage when administered at 50 mg/kg/day for 15 days. These results suggest that SR3773 may have potential for use in the treatment of human cytomegalovirus infections, but it may also exhibit renal toxicity.