1. Synthesis of dual function (5R,6R)- and (5S,6S)-5-bromo-6-methoxy-5,6-dihydro-AZT-5'-(para-bromophenyl methoxyalaninyl phosphate) as novel spermicidal and anti-HIV agents.
- Author
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Jan ST, Shih MJ, Venkatachalam TK, D'Cruz OJ, Chen CL, and Uckun FM
- Subjects
- Anti-HIV Agents chemical synthesis, Anti-HIV Agents pharmacology, Contraceptive Devices, Female, Dideoxynucleotides, Female, HIV drug effects, HIV Infections prevention & control, Humans, Male, Nonoxynol pharmacology, Organophosphorus Compounds pharmacology, Spermatocidal Agents chemical synthesis, Spermatocidal Agents pharmacology, Spermatozoa drug effects, Virus Replication drug effects, Zidovudine pharmacology, Organophosphorus Compounds chemical synthesis, Zidovudine analogs & derivatives, Zidovudine chemical synthesis
- Abstract
We synthesized a novel compound, 5-bromo-6-methoxy-5,6-dihydro-AZT-5'- (p-bromophenyl methoxyalaninyl phosphate), which had an EC50 value of 5 microM in sperm motility assays. This is > 1 log10 better than that of the detergent spermicide nonoxynol-9 (EC50 81 microM). The compound also displayed a potent anti-human immunodeficiency virus (HIV) activity with an IC50 value of 0.005 microM in HIV replication assays, which was virtually identical to that of AZT (IC50 0.006 microM) and > 2 log10 more potent than that of nonoxynol-9 (IC50 2.2 microM). The promising results reported herein recommend the further development of the dual function 5-halo-6-alkoxyl-5,6-dihydro-AZT derivatives as a new class of vaginal contraceptives capable of preventing the sexual transmission of HIV while providing fertility control for women who are at high risk of acquiring HIV by heterosexual transmission. These dual function 5-halo-6-alkoxyl-5,6-dihydro-AZT derivatives may also have utility in curbing domestic and wildlife animal retroviral transmissions.
- Published
- 1999
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