title: Design, synthesis and anticancer activity of 1-acyl-3-amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives.
abstract: A series of novel 1-acyl-3-amino-1,4,5,6-tetrahydropyrrolo[3,4-c]pyrazole derivatives were designed and synthesized. These derivatives were initially evaluated for their in vitro anticancer activity against human colon carcinoma HCT-116 cell line, and compounds 11a, b were chosen for further evaluation their in vitro activity against other five human cancer cell lines. These results indicate that most of the target compounds have considerable in vitro anticancer activity. The most active compound 11a was found to be 4- to 28-fold more potent than (R)-roscovitine against six human cancer cell lines. In addition, compound 11a was assessed for its activity against 12 kinases, and then evaluated for its interaction mode by docking experiments with cyclin-dependent kinase 5 (CDK5) and glycogen synthase kinase-3β (GSK3β).
authors.affiliation: Institute of Medicinal Biotechnology, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing 100050, PR China.
authors.forename: Xiao-Guang
authors.initials: XG
authors.lastname: Bai
authors.forename: Dong-Ke
authors.initials: DK
authors.lastname: Yu
authors.forename: Ju-Xian
authors.initials: JX
authors.lastname: Wang
authors.forename: Hao
authors.initials: H
authors.lastname: Zhang
authors.forename: Hong-Wei
authors.initials: HW
authors.lastname: He
authors.forename: Rong-Guang
authors.initials: RG
authors.lastname: Shao
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Li
authors.forename: Yu-Cheng
authors.initials: YC
authors.lastname: Wang
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000633:toxicity; D001665:Binding Sites; D045744:Cell Line, Tumor; D051360:Cyclin-Dependent Kinase 5 / Q000737:chemistry / Q000378:metabolism; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D038362:Glycogen Synthase Kinase 3 / Q000737:chemistry / Q000378:metabolism; D000071679:Glycogen Synthase Kinase 3 beta; D045325:HCT116 Cells; D006801:Humans; D062105:Molecular Docking Simulation; D011494:Protein Kinases / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011687:Purines / Q000737:chemistry / Q000633:toxicity; D011720:Pyrazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D011758:Pyrroles / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D000077546:Roscovitine; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D011687:Purines; D011720:Pyrazoles; D011758:Pyrroles; D000077546:Roscovitine; C031280:pyrazole; D011494:Protein Kinases; D051360:Cyclin-Dependent Kinase 5; C000605506:GSK3B protein, human; D000071679:Glycogen Synthase Kinase 3 beta; D038362:Glycogen Synthase Kinase 3