A series of 2',3'-unsaturated and 3'-substituted 2',3'-dideoxynucleoside analogues of purines and pyrimidines have been synthesized and evaluated for their inhibitory activity against human immunodeficiency virus (HIV). The 2',3'-unsaturated analogues of 2',3'-dideoxycytidine (ddeCyd) and 2',3'-dideoxythymidine (ddeThd), 3'-azido-2',3'-dideoxythymidine (AzddThd), 3'-fluoro-2',3'-dideoxythymidine, 2',3'-dideoxycytidine (ddCyd), and 2',3'-dideoxyadenosine (ddAdo) emerged as the most potent inhibitors of HIV-induced cytopathogenicity in the human T lymphocyte cell lines ATH8 and MT4. In ATH8 cells ddCyd, ddeCyd, and ddAdo had the highest therapeutic index whereas in MT4 cells AzddThd, ddThd, ddCyd, and ddAdo were the most selective. Derivatives from ddThd in which the substituent group was linked to the 3'-carbon atom via a thio, sulfonyl, or oxygen bridge were far less inhibitory to HIV than was AzddThd.
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Abstract (XII).
Human papillomavirus induces the hyperproliferation of epithelial cells, leading to a broad spectrum of human diseases, ranging from benign warts to malignant neoplasms, depending on the location of the lesion, the immune status of the patient and the type of human papillomavirus. Current therapies for human papillomavirus-associated diseases are based on the excision or ablation of dysplastic or malignant tissue, and are associated with a high frequency of recurrent disease, discomfort and costs. A better understanding of the viral replicative cycle and of the interaction between the virus and the host cell, particularly the cell cycle regulation, has opened new perspectives. Recently, new treatment modalities for human papillomavirus-induced lesions have been identified, including the use of antiviral/immunomodulatory therapies, such as cidofovir, antisense oligonucleotides, imiquimod and human papillomavirus vaccines.
No abstract is provided for this article.