Jan S T, Shih M J, Venkatachalam T K, D'Cruz O J, Chen C L, Uckun F M
Drug Discovery Program, Hughes Institute, St Paul, MN 55113, USA.
Antivir Chem Chemother. 1999 Jan;10(1):39-46. doi: 10.1177/095632029901000105.
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.
我们合成了一种新型化合物，5-溴-6-甲氧基-5,6-二氢-AZT-5'-（对溴苯基甲氧基丙氨酰磷酸酯），在精子活力测定中其半数有效浓度（EC50）值为5微摩尔。这比对洗涤剂杀精剂壬苯醇醚-9（EC50为81微摩尔）的效果好超过1个对数单位。该化合物在HIV复制测定中还表现出强效的抗人类免疫缺陷病毒（HIV）活性，其半数抑制浓度（IC50）值为0.005微摩尔，这与齐多夫定（AZT，IC50为0.006微摩尔）几乎相同，且比壬苯醇醚-9（IC50为2.2微摩尔）强效超过2个对数单位。本文报道的这些有前景的结果推荐进一步开发双功能的5-卤代-6-烷氧基-5,6-二氢-AZT衍生物，作为一类新型阴道避孕药，能够在为面临通过异性传播感染HIV高风险的女性提供生育控制的同时预防HIV的性传播。这些双功能的5-卤代-6-烷氧基-5,6-二氢-AZT衍生物在抑制家畜和野生动物逆转录病毒传播方面也可能有用。
