title: Synthesis of new heterocyclic compounds based on pyrazolopyridine scaffold and evaluation of their neuroprotective potential in MPP+-induced neurodegeneration.
abstract: Neurodegenerative disorders including Alzheimer's disease, Parkinson's disease, and Huntington's disease affect millions of people in the world. Thus several new approaches to treat brain disorders are under development. The aim of the present study is to synthesize potential neuroprotective heterocyclic compounds based on pyrazolopyridine derivatives and then to evaluate their effects in MPP+-induced neurodegeneration in human neuroblastoma cell line (SH-SY5Y cells). The effects of the compounds on cell viability were measured by MTT assay and the changes in apoptosis-related proteins including bax, Bcl-2, Bcl-xl and caspase-3 were investigated by western blot technique. Based on the cell viability results obtained by MTT assay, the percentage of neuroprotection-induced by compounds against MPP+-induced neurotoxicity in SH-SY5Y cells was between 20% and 30% at 5 μM concentrations of all synthesized compounds. Moreover, the downregulation in pro-apoptotic proteins including bax and caspase-3 were found following the novel synthesized compounds treatments and these effects were observed in a dose-dependent manner. Our results provide an evidence that these heterocyclic compounds based on pyrazolopyridine derivatives may have a role on dopaminergic neuroprotection via antiapoptotic pathways.
authors.affiliation: Institut de Chimie Organique et Analytique, Université d'Orléans, UMR-CNRS 7311, BP 6759, rue de Chartres, 45067, Orléans cedex 2, France; Laboratoire de Chimie Organique et Analytique, Université Sultan Moulay Slimane, Faculté des Sciences et Techniques, BP 523, 23000, Beni-Mellal, Morocco.
authors.forename: Jabrane
authors.initials: J
authors.lastname: Jouha
authors.affiliation: Institut de Chimie Organique et Analytique, Université d'Orléans, UMR-CNRS 7311, BP 6759, rue de Chartres, 45067, Orléans cedex 2, France.
authors.forename: Mohammed
authors.initials: M
authors.lastname: Loubidi
authors.affiliation: Laboratoire de Chimie Organique et Analytique, Université Sultan Moulay Slimane, Faculté des Sciences et Techniques, BP 523, 23000, Beni-Mellal, Morocco.
authors.forename: Jamila
authors.initials: J
authors.lastname: Bouali
authors.affiliation: Laboratoire de Chimie Organique et Analytique, Université Sultan Moulay Slimane, Faculté des Sciences et Techniques, BP 523, 23000, Beni-Mellal, Morocco.
authors.forename: Salha
authors.initials: S
authors.lastname: Hamri
authors.affiliation: Laboratoire de Chimie Organique et Analytique, Université Sultan Moulay Slimane, Faculté des Sciences et Techniques, BP 523, 23000, Beni-Mellal, Morocco.
authors.forename: Abderrafia
authors.initials: A
authors.lastname: Hafid
authors.affiliation: Institut de Chimie Organique et Analytique, Université d'Orléans, UMR-CNRS 7311, BP 6759, rue de Chartres, 45067, Orléans cedex 2, France.
authors.forename: Franck
authors.initials: F
authors.lastname: Suzenet
authors.affiliation: Institut de Chimie Organique et Analytique, Université d'Orléans, UMR-CNRS 7311, BP 6759, rue de Chartres, 45067, Orléans cedex 2, France.
authors.forename: Gérald
authors.initials: G
authors.lastname: Guillaumet
authors.affiliation: Department of Physiology and Center for Brain Research, Faculty of Medicine, Ege University, 35100, Bornova, Izmir, Turkey.
authors.forename: Taner
authors.initials: T
authors.lastname: Dagcı
authors.affiliation: Laboratoire de Chimie Organique et Analytique, Université Sultan Moulay Slimane, Faculté des Sciences et Techniques, BP 523, 23000, Beni-Mellal, Morocco.
authors.forename: Mostafa
authors.initials: M
authors.lastname: Khouili
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, 35100, Bornova, Izmir, Turkey.
authors.forename: Fadime
authors.initials: F
authors.lastname: Aydın
authors.affiliation: Department of Physiology and Pharmacology "Vittorio Erspamer", Sapienza University of Rome, P. le Aldo Moro 5, 00185, Rome, Italy.
authors.forename: Luciano
authors.initials: L
authors.lastname: Saso
authors.affiliation: Department of Biochemistry, Faculty of Pharmacy, Ege University, 35100, Bornova, Izmir, Turkey. Electronic address: guliz.armagan@ege.edu.tr.
authors.forename: Güliz
authors.initials: G
authors.lastname: Armagan
mesh_terms: D051017:Apoptosis Regulatory Proteins / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006571:Heterocyclic Compounds / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D009447:Neuroblastoma / Q000473:pathology; D019636:Neurodegenerative Diseases / Q000139:chemically induced / Q000188:drug therapy*; D018696:Neuroprotective Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D011720:Pyrazoles / Q000737:chemistry / Q000494:pharmacology*; D011725:Pyridines / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D051017:Apoptosis Regulatory Proteins; D006571:Heterocyclic Compounds; D018696:Neuroprotective Agents; D011720:Pyrazoles; D011725:Pyridines; C118531:pyrazolopyridine
keywords: Apoptosis; MPP(+); Neurodegeneration; Pyrazolo[3,4-b]pyridine; Suzuki-Miyaura