Leydet A, Barragan V, Boyer B, Montéro J L, Roque J P, Witvrouw M, Este J, Snoeck R, Andrei G, De Clercq E
Laboratoire de Chimie Organique Physique, Université de Montpellier II, France.
J Med Chem. 1997 Jan 31;40(3):342-9. doi: 10.1021/jm960493b.
omega-Acryloyl anionic surfactants, whose polar heads are derived from amino acids, have been telomerized to prepare polyanions of a predetermined molecular weight. The main goal of this study was to verify whether the antiviral activity is influenced by the degree of polymerization of the polyanions. The oligomeric polyanions were evaluated for their activity against human immunodeficiency virus (HIV-1 or HIV-2) and various other RNA and DNA viruses. With regard to their anti-HIV activity, a minimum number of anionic groups was necessary to achieve an inhibitory effect. Moreover, to be active the overall conformation of the polyanion must be such that the anionic groups are located on the external site of the molecule. With some of the polyanions, a 50% inhibition concentration (IC50) as low as 1 microgram/ mL, or even 0.1 microgram/mL, was noted against HIV-1 in CEM-4 and MT-4 cells, respectively. The most potent polyanions also proved active against human cytomegalovirus and herpex simplex virus at concentrations of 5-10 and 20-40 micrograms/mL, respectively. No activity was observed against any of the other viruses tested (i.e., vesicular stomatitis, Sindbis, Semliki forest, parainfluenza, Junin, Tacaribe, Coxsackie, polio, reo, and vaccinia). No toxicity for the host cells was observed at concentrations up to 200 micrograms/mL.
ω-丙烯酰基阴离子表面活性剂，其极性头部衍生自氨基酸，已被端粒化以制备具有预定分子量的聚阴离子。本研究的主要目的是验证抗病毒活性是否受聚阴离子聚合度的影响。对低聚聚阴离子针对人类免疫缺陷病毒（HIV-1或HIV-2）以及各种其他RNA和DNA病毒的活性进行了评估。关于它们的抗HIV活性，需要最少数量的阴离子基团才能实现抑制作用。此外，为了具有活性，聚阴离子的整体构象必须使阴离子基团位于分子的外部位点。对于某些聚阴离子，在CEM-4和MT-4细胞中，分别对HIV-1的50%抑制浓度（IC50）低至1微克/毫升，甚至0.1微克/毫升。最有效的聚阴离子在浓度分别为5-10微克/毫升和20-40微克/毫升时，也证明对人巨细胞病毒和单纯疱疹病毒有活性。对所测试的任何其他病毒（即水疱性口炎病毒、辛德毕斯病毒、塞姆利基森林病毒、副流感病毒、胡宁病毒、塔卡里贝病毒、柯萨奇病毒、脊髓灰质炎病毒、呼肠孤病毒和痘苗病毒）均未观察到活性。在高达200微克/毫升的浓度下，未观察到对宿主细胞的毒性。
