title: Design and synthesis of N-phenylacetyl (sulfonyl) 4,5-dihydropyrazole derivatives as potential antitumor agents.
abstract: 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.
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing 210093, PR China.
authors.forename: Xin-Hua
authors.initials: XH
authors.lastname: Liu
authors.forename: Ban-Feng
authors.initials: BF
authors.lastname: Ruan
authors.forename: Jing-Xin
authors.initials: JX
authors.lastname: Liu
authors.forename: Bao-An
authors.initials: BA
authors.lastname: Song
authors.forename: Ling-Hong
authors.initials: LH
authors.lastname: Jing
authors.forename: Jun
authors.initials: J
authors.lastname: Li
authors.forename: Yang
authors.initials: Y
authors.lastname: Yang
authors.forename: Hai-Liang
authors.initials: HL
authors.lastname: Zhu
authors.forename: Xing-Bao
authors.initials: XB
authors.lastname: Qi
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002460:Cell Line; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015195:Drug Design; D006801:Humans; D020128:Inhibitory Concentration 50; D008958:Models, Molecular; D015394:Molecular Structure; D011720:Pyrazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019098:Telomerase / Q000037:antagonists & inhibitors
chemical_list: D000970:Antineoplastic Agents; D011720:Pyrazoles; D019098:Telomerase