State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
Bioorg Med Chem Lett. 2011 May 15;21(10):2916-20. doi: 10.1016/j.bmcl.2011.03.066. Epub 2011 Mar 23.
A series of novel N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassay tests show that compound 4a exhibited high activity against human gastric cancer cell SGC-7901, liver cancer Hep-G2 and human prostate PC-3 cell lines with IC(50) values of 21.23±0.99, 29.43±0.32 and 30.89±1.07 μM, respectively. All title compounds were assayed for telomerase inhibition by a modified TRAP assay, the results show that compound 4a can inhibit telomerase with IC(50) value of 4.0±0.32 μM. Docking simulation was performed to position compound 4a into the telomerase (3DU6) active site to determine the probable binding model.
一系列新型 N-苯乙酰（磺酰基）4,5-二氢吡唑衍生物被合成出来作为潜在的端粒酶抑制剂。生物测定试验表明，化合物 4a 对人胃癌细胞 SGC-7901、肝癌 Hep-G2 和人前列腺 PC-3 细胞系表现出高活性，IC50 值分别为 21.23±0.99、29.43±0.32 和 30.89±1.07 μM。所有标题化合物均通过改良的 TRAP 测定法进行端粒酶抑制试验，结果表明化合物 4a 能以 4.0±0.32 μM 的 IC50 值抑制端粒酶。对接模拟将化合物 4a 定位到端粒酶（3DU6）活性部位以确定可能的结合模型。
