Institute of Biomaterials and Bioengineering, Tokyo Medical and Dental University, Chiyoda-ku, Tokyo, Japan.
Bioorg Med Chem. 2011 Nov 15;19(22):6735-42. doi: 10.1016/j.bmc.2011.09.045. Epub 2011 Sep 29.
Derivatives of CD4 mimics were designed and synthesized to interact with the conserved residues of the Phe43 cavity in gp120 to investigate their anti-HIV activity, cytotoxicity, and CD4 mimicry effects on conformational changes of gp120. Significant potency gains were made by installation of bulky hydrophobic groups into the piperidine moiety, resulting in discovery of a potent compound with a higher selective index and CD4 mimicry. The current study identified a novel lead compound 11 with significant anti-HIV activity and lower cytotoxicity than those of known CD4 mimics.
设计并合成了 CD4 模拟物的衍生物，以与 gp120 中 Phe43 腔的保守残基相互作用，研究其抗 HIV 活性、细胞毒性以及对 gp120 构象变化的 CD4 模拟作用。通过在哌啶部分引入大体积疏水基团，显著提高了化合物的活性，发现了一种具有更高选择性指数和 CD4 模拟作用的有效化合物。本研究鉴定了一种新型先导化合物 11，其抗 HIV 活性显著高于已知的 CD4 模拟物，细胞毒性较低。
