Department of Biomedical and Pharmaceutical Sciences, College of Pharmacy, University of Rhode Island, Kingston, RI 02881, USA.
Med Chem. 2012 Mar;8(2):193-7. doi: 10.2174/157340612800493737.
Conjugates between suramin, a polyanionic naphthalene sulfonate derivative, and nucleoside reverse transcriptase inhibitors (NRTIs), 3'-azido-2',3'-dideoxythymidine (AZT) and 3'-fluoro-2',3'-dideoxythymidine (FLT), were designed to create an antiretroviral with multiple mechanisms of action that could be developed as an anti-HIV topical microbicide candidate. The anti-HIV activity of these conjugates was compared with that of suramin and the corresponding physical mixtures of suramin and nucleosides. The conjugates were synthesized as sulfonate esters by reaction of suramin with the nucleoside analogs in the presence of phosphorus pentoxide, and were tested against X4 and R5 labadapted strains of HIV-1. Suramin conjugates of AZT (EC50= 19.4 μg/ml) and FLT (EC50= 23.6 μg/ml) demonstrated improved anti-HIV activity against X4 strain of virus by 2.5 and 2 fold, respectively, when compared with suramin. The physical mixtures of suramin with nucleosides significantly improved anti-HIV activity of suramin against X4 strain by more than 55 fold.
将苏拉明（一种多阴离子萘磺酸盐衍生物）与核苷逆转录酶抑制剂（NRTIs），即 3'-叠氮-2',3'-双脱氧胸苷（AZT）和 3'-氟-2',3'-双脱氧胸苷（FLT）缀合，旨在创造一种具有多种作用机制的抗逆转录病毒药物，可开发为抗 HIV 局部杀微生物候选药物。这些缀合物的抗 HIV 活性与苏拉明和苏拉明与核苷的相应物理混合物进行了比较。通过在五氧化二磷存在下将苏拉明与核苷类似物反应，将缀合物合成磺酸盐酯，并对 X4 和 R5 实验室适应的 HIV-1 株进行了测试。与苏拉明相比，AZT（EC50=19.4μg/ml）和 FLT（EC50=23.6μg/ml）的苏拉明缀合物对 X4 株病毒的抗 HIV 活性分别提高了 2.5 倍和 2 倍。苏拉明与核苷的物理混合物使苏拉明对 X4 株病毒的抗 HIV 活性显著提高了 55 倍以上。
