Stampidine: a selective oculo-genital microbicide.
Stampidine: a selective oculo-genital microbicide.
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Stampidine：一种选择性眼生殖器杀菌剂。
DOI：
10.1093/jac/dki168
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Uckun,FatihM
中科院分区：
文献类型：
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作者：
D'Cruz,OsmondJ;Uckun,FatihM
腺病毒（ADVs）是与结膜炎、生殖器溃疡和尿道炎相关的严重和极具传染性的眼部和生殖器感染的病原体。然而，目前还没有针对腺病毒感染的功能性抗病毒化合物。我们发现了司他夫定卤素取代苯基磷酰胺衍生物（STV/d4T）作为一类新的双功能抗人类免疫缺陷病毒（HIV）药物，具有强效和选择性的抗adv活性。先导化合物stampidine[5 ' -（4-溴苯基甲氧基磷酸）-2 ',3 ' -二脱氢-3 ' -脱氧胸腺嘧啶]是最有效的无毒双功能抗病毒药物。Stampidine对药物敏感和耐药的HIV毒株均表现出显著的体外和体内抗HIV活性。Stampidine对粘膜上皮细胞无细胞毒性和刺激性。到目前为止进行的几项临床前研究表明，stampidine具有作为预防和/或有效治疗眼生殖器ADV/HIV感染的双重功能外用药物的临床潜力。
Adenoviruses (ADVs) are causative agents of severe and extremely contagious ocular and genital infections associated with conjunctivitis, genital ulcers and urethritis. Yet, no functional antiviral compounds are currently available against adenoviral infections. We discovered halogen-substituted phenyl phosphoramidate derivatives of stavudine (STV/d4T) as a new class of dual-function anti-human immunodeficiency virus (HIV) agents with potent and selective anti-ADV activity. The lead compound, stampidine [5′-(4-bromophenyl methoxyalaninylphosphate)-2′,3′-didehydro-3′-deoxythymidine], was the most potent non-toxic dual-function antiviral agent. Stampidine displayed remarkablein vitroandin vivoanti-HIV activity against drug-sensitive and drug-resistant HIV strains. Stampidine was non-cytotoxic and nonirritating to mucosal epithelial cells. Several preclinical studies conducted thus far, suggest that stampidine has clinical potential as a dual-function topical agent for the prevention and/or effective treatment of oculo-genital ADV/HIV infections.