二芳基胺类抗肿瘤先导物的结构修饰和活性评价

Synthesis and biological evaluation of diarylamines with antitumor activity

摘要:
对二芳基胺类抗肿瘤先导物1～3进行多位点结构修饰, 设计合成了18个二芳基胺类衍生物, 并在人肿瘤细胞系A549、DU145、KB和KB-vin上进行了抗肿瘤活性评价, 发现化合物A6和B2具有较强的抑制肿瘤细胞生长活性 (GI₅₀ 1.55～2.10 μmol·L⁻¹), 化合物A9可选择性地抑制KB, KB-vin和DU145肿瘤细胞生长 (GI₅₀ 1.10～2.00 μmol·L⁻¹)。获知的构效关系为进一步结构优化奠定了基础。

Abstract:
By structural modifications of our previous leads 1−3, 18 diarylamines were designed, synthesized and evaluated with a human tumor cell line panel, including A549, DU145, KB, and KB-vin cell lines, resulting in the discovery of new antitumor agents A6 and B2 with low micromolar GI₅₀ values ranging from 1.55−2.10 μmol·L⁻¹ for above cell lines, and A9 with GI₅₀ values ranging from 1.55−2.10 μmol·L⁻¹ specially for DU145, KB, and KB-vin cells. Current structure-activity relationships are helpful for further lead optimization.