title: Stampidine: a selective oculo-genital microbicide.
abstract: 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 remarkable in vitro and in vivo anti-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.
authors.affiliation: Parker Hughes Institute, St Paul, MN 55113, USA. odcruz@ih.org
authors.forename: Osmond J
authors.initials: OJ
authors.lastname: D'Cruz
authors.forename: Fatih M
authors.initials: FM
authors.lastname: Uckun
mesh_terms: D000256:Adenoviridae / Q000145:classification / Q000187:drug effects*; D000818:Animals; D019380:Anti-HIV Agents / Q000494:pharmacology*; D000998:Antiviral Agents / Q000494:pharmacology*; D054306:Dideoxynucleotides; D004355:Drug Stability; D015828:Eye Infections, Viral / Q000188:drug therapy*; D005835:Genitalia / Q000821:virology*; D006801:Humans; D011991:Receptors, Virus / Q000032:analysis; D012703:Serotyping; D012995:Solubility; D018119:Stavudine / Q000031:analogs & derivatives* / Q000494:pharmacology; D013938:Thymidine Monophosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D014526:Urethritis / Q000188:drug therapy
chemical_list: D019380:Anti-HIV Agents; D000998:Antiviral Agents; D054306:Dideoxynucleotides; D011991:Receptors, Virus; C085301:adenovirus receptor; C472384:stampidine; D013938:Thymidine Monophosphate; D018119:Stavudine