Polyanion inhibitors of HIV and other viruses. 7. Polyanionic compounds and polyzwitterionic compounds derived from cyclodextrins as inhibitors of HIV transmission
Polyanion inhibitors of HIV and other viruses. 7. Polyanionic compounds and polyzwitterionic compounds derived from cyclodextrins as inhibitors of HIV transmission
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DOI：
10.1021/jm970661f
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发表时间：
1998-12-03
影响因子：
7.3
通讯作者：
De Clercq, E
中科院分区：
文献类型：
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作者：
Leydet, A;Moullet, C;De Clercq, E
以α， α′-偶氮双（异丁腈）为催化剂，在紫外照射下，硫硫酸和巯基丙酸在环糊精（CDs）上自由基加成，得到了新的聚阴离子化合物。所有这些含有18-48个羧酸基团的多阴离子，在0.1-2.9 μ M的50%抑制浓度（IC50）下抑制MT-4细胞中人类免疫缺陷病毒1型（HIV-1）株IIIB的复制，而在高达62 μ M的浓度下对宿主细胞无毒。这些化合物对临床HIV-1分离物（HE）也有活性，浓度大于或等于4倍。只有一些化合物对两种HIV-2菌株（ROD和EHO）有活性，但浓度高于抑制HIV-1 （IIIB和HE）复制所需的浓度。此外，这些化合物对嗜m型HIV-1株Bat没有活性，但对猴免疫缺陷病毒(SIV （MAC(251)）有活性。这些化合物对人巨细胞病毒的复制也有抑制作用，其IC50值为1-10 μ M，但对单纯疱疹病毒（1型和2型）或其他病毒（picorna-, toga-, reo-, orthymxo -，副ymxo -， bunya-， rhabdo-和痘病毒）没有抑制作用。自由基加成在受保护的半胱氨酸的聚丙烯化CDs上得到多两性离子化合物。最后这些化合物都没有证明对HIV-1、HIV-2或任何其他测试病毒的复制有抑制作用。
New polyanionic compounds were obtained from radical addition of thiomalic acid and mercaptopropionic acid onto perallylated cyclodextrins (CDs) under UV irradiation with a catalytic amount of alpha,alpha'-azobis(isobutyronitrile). All these polyanions, bearing 18-48 carboxylate groups, inhibited human immunodeficiency virus type 1 (HIV-1) strain IIIB replication in MT-4 cells at a 50% inhibitory concentration (IC50) of 0.1-2.9 mu M, while not being toxic to the host cells at concentrations up to 62 mu M. These compounds were also active against a clinical HIV-1 isolate (HE) at greater than or equal to 4-fold higher concentrations. Only some compounds showed activity against the two HIV-2 strains (ROD and EHO) but at higher concentrations than those required to inhibit HIV-1 (IIIB and HE) replication. In addition, these compounds were not active against the M-tropic HIV-1 strain Bat but were active against simian immunodeficiency virus [SIV (MAC(251))]. These compounds were also inhibitory to the replication of human cytomegalovirus at an IC50 of 1-10 mu M, but not herpes simplex virus (type 1 and type 2) or other (picorna-, toga-, reo-, orthomyxo-, paramyxo-, bunya-, rhabdo-, and poxvirus) viruses. Radical addition on perallylated CDs of a protected cysteine gave polyzwitterionic compounds. None of these last compounds proved inhibitory to the replication of HIV-1, HIV-2, or any of the other viruses tested.