1310098-53-3Relevant academic research and scientific papers
Dihydropyrazole derivatives as telomerase inhibitors: Structure-based design, synthesis, SAR and anticancer evaluation in vitro and in vivo
Wang, Yang,Cheng, Fei Xiong,Yuan, Xiao Long,Tang, Wen Jian,Shi, Jing Bo,Liao, Chen Zhong,Liu, Xin Hua
, p. 231 - 251 (2016/05/02)
It is of our interest to generate and identify novel compounds with regulation telomerase for cancer therapy. In order to carry out more rational design, based on structure-based drug design, several series of N-substituted-dihydropyrazole derivatives, totally 78 compounds as potential human telomerase inhibitors were designed and synthesized. The results demonstrated that some compounds had potent anticancer activity against four tumor cell lines, and showed good selectivity on tumor cells over somatic cells. By the modified TRAP assay, compound 13i exhibited the most potent inhibitory activity against telomerase with an IC50 value of 0.98 μM. In vivo evaluation results indicated that compound 13i could inhibit growth of S180 and HepG2 tumor-bearing mice, and it also significantly enhanced the survival rate of EAC tumor-bearing mice. The further results in vivo confirmed that it could significantly improve pathological changes of N,N-diethylnitrosamine (DEN)-induced rat hepatic tumor. These data support further studies to assess rational design of more efficient telomerase inhibitors in the future.
Design and synthesis of N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents
Liu, Xin-Hua,Ruan, Ban-Feng,Liu, Jing-Xin,Song, Bao-An,Jing, Ling-Hong,Li, Jun,Yang, Yang,Zhu, Hai-Liang,Qi, Xing-Bao
experimental part, p. 2916 - 2920 (2011/06/26)
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 IC50 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.
