Centro de Química Medicinal da Universidade do Porto, Rua de Jorge Viterbo Ferreira no. 228, 4050-313 Porto, Portugal.
Bioorg Med Chem. 2013 Jun 1;21(11):2941-59. doi: 10.1016/j.bmc.2013.03.079. Epub 2013 Apr 6.
A promising antitumor xanthone derivative was optimized following a multidimensional approach that involved the synthesis of 17 analogues, the study of their lipophilicity and solubility, and the evaluation of their growth inhibitory activity on four human tumor cell lines. A new synthetic route for the hit xanthone derivative was also developed and applied for the synthesis of its analogues. Among the used cell lines, the HL-60 showed to be in general more sensitive to the compounds tested, with the most potent compound having a GI50 of 5.1 μM, lower than the hit compound. Lipophilicity was evaluated by the partition coefficient (K(p)) of a solute between buffer and two membrane models, namely liposomes and micelles. The compounds showed a logK(p) between 3 and 5 and the two membrane models showed a good correlation (r(2)=0.916) between each other. Studies concerning relationship between solubility and structure were developed for the hit compound and 5 of its analogues.
一种有前景的抗肿瘤酮衍生物通过多维方法进行了优化，该方法包括合成 17 种类似物、研究它们的亲脂性和溶解度，并评估它们对四种人肿瘤细胞系的生长抑制活性。还开发了一种针对命中酮衍生物的新合成路线，并将其应用于类似物的合成。在所使用的细胞系中，HL-60 通常对测试的化合物更为敏感，最有效的化合物的 GI50 为 5.1 μM，低于命中化合物。亲脂性通过溶质在缓冲液和两种膜模型（即脂质体和胶束）之间的分配系数（K(p)）来评估。这些化合物的 logK(p) 值在 3 到 5 之间，并且两种膜模型之间具有很好的相关性（r(2)=0.916）。对命中化合物及其 5 种类似物的溶解度与结构之间的关系进行了研究。
