Meyer K L, Marasco C J, Morris-Natschke S L, Ishaq K S, Piantadosi C
University of North Carolina, School of Pharmacy, Division of Medicinal Chemistry and Natural Products, Chapel Hill 27599.
J Med Chem. 1991 Apr;34(4):1377-83. doi: 10.1021/jm00108a021.
A series of synthetic lipids containing a two- or three-carbon backbone substituted with a thio, oxy, or amidoalkyl functionality and either a phosphocholine or quaternary ammonium moiety was evaluated as potential anti-HIV-1 agents. Several analogues were identified as possessing activity with the most promising compound being rac-3-octadecanamido-2-ethoxypropylphosphocholine (8). Compound 8 exhibited an IC50 for the inhibition of plaque formation of 0.16 microM which was 84-fold lower than the IC50 value determined for CEM-SS cell growth inhibition. Initial mechanistic studies have indicated that these compounds, unlike AZT, are not reverse transcriptase (RT) inhibitors, but instead appear to inhibit a late step in HIV replication involving virus assembly and infectious virus production. Since these lipids are acting via a different mechanism, they represent an alternative approach to the chemotherapeutic treatment of AIDS as well as candidates for combination therapy with AZT.
一系列含有被硫代、氧基或酰胺烷基官能团取代的二碳或三碳主链以及磷酸胆碱或季铵部分的合成脂质被评估为潜在的抗HIV-1药物。鉴定出几种类似物具有活性，其中最有前景的化合物是rac-3-十八烷酰胺基-2-乙氧基丙基磷酸胆碱（8）。化合物8对斑块形成抑制的IC50为0.16微摩尔，比针对CEM-SS细胞生长抑制测定的IC50值低84倍。初步的机制研究表明，这些化合物与齐多夫定不同，不是逆转录酶（RT）抑制剂，而是似乎抑制HIV复制中涉及病毒组装和感染性病毒产生的后期步骤。由于这些脂质通过不同的机制起作用，它们代表了一种治疗艾滋病的替代化疗方法以及与齐多夫定联合治疗的候选药物。
