title: Synthesis, biological evaluation, 3D-QSAR studies of novel aryl-2H-pyrazole derivatives as telomerase inhibitors.
abstract: A series of novel aryl-2H-pyrazole derivatives bearing 1,4-benzodioxan or 1,3-benzodioxole moiety were designed as potential telomerase inhibitors to enhance the ability of aryl-2H-pyrazole derivatives to inhibit telomerase, a target of anticancer. The telomerase inhibition tests showed that compound 16A displayed the most potent inhibitory activity with IC(50) value of 0.9 μM for telomerase. The antiproliferative tests showed that compound 16A exhibited high activity against human gastric cancer cell SGC-7901 and human melanoma cell B16-F10 with IC(50) values of 18.07 and 5.34 μM, respectively. Docking simulation showed that compound 16A could bind well with the telomerase active site and act as telomerase inhibitor. 3D-QSAR model was also built to provide more pharmacophore understanding that could be used to design new agents with more potent telomerase inhibitory activity.
authors: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, P.R. China.
authors: Yin
authors: Y
authors: Luo
authors: Shuai
authors: S
authors: Zhang
authors: Ke-Ming
authors: KM
authors: Qiu
authors: Zhi-Jun
authors: ZJ
authors: Liu
authors: Yu-Shun
authors: YS
authors: Yang
authors: Jie
authors: J
authors: Fu
authors: Wei-Qing
authors: WQ
authors: Zhong
authors: Hai-Liang
authors: HL
authors: Zhu
mesh_terms: D001665:Binding Sites; D048708:Cell Growth Processes / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008958:Models, Molecular; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D019098:Telomerase / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D004791:Enzyme Inhibitors; D011720:Pyrazoles; D019098:Telomerase