State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem. 2013 Jan 15;21(2):448-55. doi: 10.1016/j.bmc.2012.11.020. Epub 2012 Nov 24.
A series of novel thiazolyl-pyrazoline derivatives containing benzodioxole (C1-C20) have been designed and synthesized. Among of the synthesized compounds, 2-(5-(benzo[d][1,3]dioxol-5-yl)-3-(4-bromophenyl)-4,5-dihydro-1H-pyrazol-1-yl)-4-(4-bromophenyl)thiazole (C6) displayed the most potent inhibitory activity for HER-2 (IC(50) = 0.18 μM for HER-2). Antiproliferative assay results indicated that compound C6 owned high antiproliferative activity against MCF-7 and B16-F10 in vitro, with IC(50) value of 0.09 and 0.12 μM, respectively, being comparable with the positive control Erlotinib. Docking simulation was further performed to determine the probable binding model. Based on the preliminary results, compound C6 with potent inhibitory activity in tumor growth would be a potential anticancer agent.
一系列含有苯并二恶烷（C1-C20）的新型噻唑基-吡唑啉衍生物被设计和合成。在所合成的化合物中，2-（5-（苯并[d][1,3]二恶烷-5-基）-3-（4-溴苯基）-4,5-二氢-1H-吡唑-1-基）-4-（4-溴苯基）噻唑（C6）对 HER-2 的抑制活性最强（对 HER-2 的 IC50 = 0.18 μM）。增殖抑制试验结果表明，化合物 C6 在体外对 MCF-7 和 B16-F10 具有高增殖抑制活性，IC50 值分别为 0.09 和 0.12 μM，与阳性对照药厄洛替尼相当。进一步进行了对接模拟以确定可能的结合模型。基于初步结果，具有肿瘤生长抑制活性的化合物 C6 可能成为一种潜在的抗癌药物。
