title: Design, synthesis and biological evaluation of pyridazino[3,4,5-de]quinazolin-3(2H)-one as a new class of PARP-1 inhibitors.
abstract: A series of pyridazino[3,4,5-de]quinazolin-3(2H)-one derivatives were designed and synthesized as PARP-1 inhibitors. Most of the synthesized compounds showed good inhibitory activities of PARP-1 and four of them achieved at the IC50 values ranging from 0.0914 μM to 0.244 μM. Two compounds, 1a and 1b, were further tested for their neuroprotective effect in the PC12 cell model injured by H2O2 and both of them exhibited excellent activities.
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Jie
authors.initials: J
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Hailiang
authors.initials: H
authors.lastname: Tan
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Qi
authors.initials: Q
authors.lastname: Sun
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Zemei
authors.initials: Z
authors.lastname: Ge
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China.
authors.forename: Xin
authors.initials: X
authors.lastname: Wang
authors.affiliation: Department of Molecular and Cellular Pharmacology, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China. Electronic address: wangyinye@bjmu.edu.cn.
authors.forename: Yinye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, PR China. Electronic address: lirt@bjmu.edu.cn.
authors.forename: Runtao
authors.initials: R
authors.lastname: Li
mesh_terms: D000818:Animals; D020134:Catalytic Domain; D015195:Drug Design; D008958:Models, Molecular; D015394:Molecular Structure; D018696:Neuroprotective Agents / Q000737:chemistry / Q000494:pharmacology; D016716:PC12 Cells; D000067856:Poly(ADP-ribose) Polymerase Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism*; D011485:Protein Binding; D011724:Pyridazines / Q000737:chemistry / Q000494:pharmacology*; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology*; D051381:Rats
chemical_list: C000604941:8-(p-tolyl)-2H-pyridazino(3,4,5-de)quinazolin-3(9H)-one; C000604942:8-phenyl-2H-pyridazino(3,4,5-de)quinazolin-3(9H)-one; D018696:Neuroprotective Agents; D000067856:Poly(ADP-ribose) Polymerase Inhibitors; D011724:Pyridazines; D011799:Quinazolines; D011065:Poly(ADP-ribose) Polymerases
keywords: Combination strategy; Molecular docking; Neuroprotectivity; PARP-1 inhibitor; Pyridazino[3,4,5-de]quinazolin-3(2H)-one