The antiproliferative activities of new substituted tetrahydroisoquinolines (THIQs) are described. Their cytotoxicities against Ishikawa human endometrial cell line were determined after 72 h drug expose employing Celtiter-Glo assay at concentrations ranging from 0.01 to 100,000 nM. The antiproliferative activities of the compounds understudy were compared to tamoxifen (TAM). In-vitro results indicated that most of the compounds showed better activity than TAM. The most active compounds obtained in this study were 1, 2, 3 and 22 whose IC50 values are 1.41, 0.91, 0.74 and 0.36 μM respectively. This study helped us to evaluate the risk of developing endometrial cancer in the design of non-steroid estrogen receptor modulators with no agonistic effects on uterus. In-silico pharmacophore hypotheses were generated using GALAHAD and PHASE and the best models with a probable bioactive conformation(s) for these compounds were proposed. These conformations and the alignments of the molecular structures give us an insight in designing compounds with better biological activity.

中文翻译：

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新型四氢异喹啉 (THIQ) 对 Ishikawa 细胞及其 3D 药效团模型的体外抗增殖活性

描述了新的取代四氢异喹啉 (THIQ) 的抗增殖活性。它们对 Ishikawa 人子宫内膜细胞系的细胞毒性在药物暴露 72 小时后使用 Celtiter-Glo 测定法测定，浓度范围为 0.01 至 100,000 nM。将研究中的化合物的抗增殖活性与他莫昔芬 (TAM) 进行比较。体外结果表明，大多数化合物显示出比 TAM 更好的活性。本研究中获得的活性最强的化合物是 1、2、3 和 22，其 IC50 值分别为 1.41、0.91、0.74 和 0.36 μM。这项研究帮助我们评估了在设计对子宫没有激动作用的非类固醇雌激素受体调节剂时发生子宫内膜癌的风险。使用 GALAHAD 和 PHASE 生成了计算机内药效团假设，并提出了具有这些化合物可能的生物活性构象的最佳模型。这些构象和分子结构的排列使我们深入了解设计具有更好生物活性的化合物。