Cushman M, Kanamathareddy S, De Clercq E, Schols D, Goldman M E, Bowen J A
Department of Medicinal Chemistry and Pharmacognosy, School of Pharmacy and Pharmacal Sciences, Purdue University, West Lafayette, Indiana 47097.
J Med Chem. 1991 Jan;34(1):337-42. doi: 10.1021/jm00105a053.
Several compounds corresponding to fragments of the schematic representation of the polymeric structure of aurintricarboxylic acid (ATA) have been prepared and tested for prevention of the cytopathic effect of HIV-1 and HIV-2 in MT-4 cell culture and HIV-1 in CEM cell culture. Both the triphenylcarbinol 3 as well as the triphenylmethane 5 were found to afford protection against the cytopathogenicity of HIV-2 in MT-4 cells and HIV-1 in CEM cells, but they were inactive against HIV-1 in MT-4 cells. Both substances were also found to inhibit syncytium formation when MOLT-4 cells were cocultured with HIV-2-infected HUT-78 cells, but were inactive in this assay against HIV-1-infected cells. When observed, the activity is generally moderate in degree of protection and requires concentrations in the 10(-4) molar range. In contrast to ATA, both of these substances were inactive when tested for prevention of the binding of the OKT4A monoclonal antibody to the CD4 receptor and also for inhibition of HIV-1 reverse transcriptase. These substances therefore appear act by a mechanism that is distinct from that of polymeric ATA. Several active and inactive structural analogues of 3 and 5 were also synthesized. The anti-HIV activity in this series seems to depend on the presence of anionic carboxylate groups, since the methyl esters 4, 6, and 12 were uniformly inactive. The diphenylmethanes 8, 14, 18, and 19 also reproducibly inhibited the cytopathic effect of HIV-1 in CEM cell culture.
已制备了几种与金精三羧酸（ATA）聚合物结构示意图片段相对应的化合物，并测试了它们在MT - 4细胞培养中预防HIV - 1和HIV - 2细胞病变效应以及在CEM细胞培养中预防HIV - 1细胞病变效应的能力。发现三苯甲醇3以及三苯甲烷5均能在MT - 4细胞中抵御HIV - 2的细胞致病性，并在CEM细胞中抵御HIV - 1的细胞致病性，但它们对MT - 4细胞中的HIV - 1无活性。还发现当MOLT - 4细胞与感染HIV - 2的HUT - 78细胞共培养时，这两种物质均能抑制合胞体形成，但在此试验中对感染HIV - 1的细胞无活性。观察到的活性在保护程度上通常适中，且所需浓度在10⁻⁴摩尔范围内。与ATA不同，这两种物质在测试预防OKT4A单克隆抗体与CD4受体结合以及抑制HIV - 1逆转录酶时均无活性。因此，这些物质似乎通过一种与聚合型ATA不同的机制发挥作用。还合成了3和5的几种活性和非活性结构类似物。该系列中的抗HIV活性似乎取决于阴离子羧酸盐基团的存在，因为甲酯4、6和12均无活性。二苯甲烷8、14、18和19在CEM细胞培养中也能可重复地抑制HIV - 1的细胞病变效应。
