title: Design and synthesis of novel 5-phenyl-N-piperidine ethanone containing 4,5-dihydropyrazole derivatives as potential antitumor agents.
abstract: 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 IC(50) 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.
authors.affiliation: School of Pharmacy, Anhui Medical University, Hefei 230032, PR China. xhliuhx@163.com
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Jing Bo
authors.initials: JB
authors.lastname: Shi
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Song
authors.forename: Xing-Bao
authors.initials: XB
authors.lastname: Qi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D060326:Chemistry Techniques, Synthetic / Q000379:methods*; D015195:Drug Design; D004980:Ethane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D008958:Models, Molecular; D010880:Piperidines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D011720:Pyrazoles / Q000737:chemistry*; D019098:Telomerase / Q000037:antagonists & inhibitors / Q000737:chemistry
chemical_list: C574521:5-phenyl-N-piperidine ethanone; D000970:Antineoplastic Agents; D010880:Piperidines; D011720:Pyrazoles; D019098:Telomerase; D004980:Ethane