Mohan P, Singh R, Baba M
Department of Medicinal Chemistry and Pharmacognosy (M/C 781), College of Pharmacy, University of Illinois, Chicago 60680.
J Med Chem. 1991 Jan;34(1):212-7. doi: 10.1021/jm00105a033.
Certain naphthalenesulfonic acid analogues have been synthesized and evaluated for their inhibitory effects on HIV-1- and HIV-2-induced cytopathogenicity, HIV-1 giant cell formation, and HIV-1 reverse transcriptase (RT) activity. A bis(naphthalenedisulfonic acid) derivative having a biphenyl spacer emerged as the most potent and selective inhibitor of virus-induced cytopathogenicity in MT-4 cells. The ED50 values for this compound were 7.6 and 36 microM for HIV-1 and HIV-2, respectively. No toxicity to the host cells was detected at 98 microM. This compound also inhibited giant cell formation and was superseded in potency by a bis(naphthalenedisulfonic acid) derivative having a flexible decamethylene spacer. In the cell-free RT assay, a long-chain amide derivative exhibited the most inhibition of RT. All the compounds that achieved complete inhibition of virus-induced cytopathogenicity at concentrations not toxic to host cells were derivatives of 4-amino-5-hydroxy-2,7- naphthalenedisulfonic acid. These analogues represent new leads for the development of anti-HIV agents.
已合成了某些萘磺酸类似物，并评估了它们对HIV-1和HIV-2诱导的细胞病变效应、HIV-1巨细胞形成以及HIV-1逆转录酶（RT）活性的抑制作用。一种具有联苯间隔基的双（萘二磺酸）衍生物成为MT-4细胞中病毒诱导的细胞病变效应最有效且最具选择性的抑制剂。该化合物对HIV-1和HIV-2的半数有效剂量（ED50）值分别为7.6和36微摩尔。在98微摩尔浓度下未检测到对宿主细胞的毒性。该化合物还抑制巨细胞形成，并且在效力上被一种具有柔性十亚甲基间隔基的双（萘二磺酸）衍生物所取代。在无细胞RT测定中，一种长链酰胺衍生物对RT的抑制作用最强。所有在对宿主细胞无毒的浓度下实现对病毒诱导的细胞病变效应完全抑制的化合物均为4-氨基-5-羟基-2,7-萘二磺酸的衍生物。这些类似物代表了抗HIV药物开发的新线索。
