کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
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1399423 | 1501165 | 2012 | 6 صفحه PDF | دانلود رایگان |

A series of novel 5-phenyl-N-piperidine ethanone-4,5-dihydropyrazole derivatives as potential telomerase inhibitors were synthesized. The bioassays demonstrated that compounds 4d, 4f, 7a and 7b occupied high antiproliferative activities against SGC-7901, MGC-803 and Bcap-37 cell lines. By a modified TRAP assay, some titled compounds were tested against telomerase, and compound 7b showed the most potent inhibitory activity with IC50 value at 2.00 ± 0.40 μM. The active compound 4d was also docked into the telomerase TERT active site to determine the probable binding model. The results indicated that conserved residues Lys189, Asp254 and Gln308 were important for ligand binding via hydrogen bond interactions.
Graphical AbstractNovel dihydropyrazole-piperidine ethanone derivatives as potential telomerase inhibitors were synthesized. Titled compound 7b showed the most potent inhibitory activity. Docking results indicated that conserved residues Lys189, Asp254 and Gln308 were important for ligand binding.Figure optionsDownload as PowerPoint slideHighlights
► Novel dihydropyrazole-piperidines were designed and two of them were determined by X-ray.
► Their antiproliferative activities against MGC-803, Bcap-37 and SGC-7901 were evaluated.
► Compound 7b showed the most potent inhibitory activity.
► Docking result indicated that residues Lys189, Asp254, Gln308 were important for ligand binding.
Journal: European Journal of Medicinal Chemistry - Volume 51, May 2012, Pages 294–299