Compounds > 5-((4-prop-2-ynylpiperazin-1-yl)methyl)quinolin-8-ol

5-((4-prop-2-ynylpiperazin-1-yl)methyl)quinolin-8-ol and linsidomine

5-((4-prop-2-ynylpiperazin-1-yl)methyl)quinolin-8-ol has been researched along with linsidomine* in 1 studies

Other Studies

1 other study(ies) available for 5-((4-prop-2-ynylpiperazin-1-yl)methyl)quinolin-8-ol and linsidomine

Article	Year
Neuroprotective and neuritogenic activities of novel multimodal iron-chelating drugs in motor-neuron-like NSC-34 cells and transgenic mouse model of amyotrophic lateral sclerosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009, Volume: 23, Issue:11 Novel therapeutic approaches for the treatment of neurodegenerative disorders comprise drug candidates designed specifically to act on multiple central nervous system targets. We have recently synthesized multifunctional, nontoxic, brain-permeable iron-chelating drugs, M30 and HLA20, possessing the N-propargylamine neuroprotective moiety of rasagiline (Azilect) and the iron-chelating moiety of VK28. The present study demonstrates that M30 and HLA20 possess a wide range of pharmacological activities in mouse NSC-34 motor neuron cells, including neuroprotective effects against hydrogen peroxide- and 3-morpholinosydnonimine-induced neurotoxicity, induction of differentiation, and up-regulation of hypoxia-inducible factor (HIF)-1alpha and HIF-target genes (enolase1 and vascular endothelial growth factor). Both compounds induced NSC-34 neuritogenesis, accompanied by a marked increase in the expression of brain-derived neurotrophic factor and growth-associated protein-43, which was inhibited by PD98059 and GF109203X, indicating the involvement of mitogen-activated protein kinase and protein kinase C pathways. A major finding was the ability of M30 to significantly extend the survival of G93A-SOD1 amyotrophic lateral sclerosis mice and delay the onset of the disease. These properties of the novel multimodal iron-chelating drugs possessing neuroprotective/neuritogenic activities may offer future therapeutic possibilities for motor neurodegenerative diseases. Topics: Amyotrophic Lateral Sclerosis; Animals; Apoptosis; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Line; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; GAP-43 Protein; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hydrogen Peroxide; Hydroxyquinolines; Hypoxia-Inducible Factor 1, alpha Subunit; Iron Chelating Agents; Mice; Mice, Transgenic; Molsidomine; Motor Neurons; Neurites; Neuroprotective Agents; Phosphopyruvate Hydratase; Piperazines; Proto-Oncogene Proteins c-akt; Receptors, Transferrin; Signal Transduction; Superoxide Dismutase; Superoxide Dismutase-1; Vascular Endothelial Growth Factor A	2009

Article

Year

Neuroprotective and neuritogenic activities of novel multimodal iron-chelating drugs in motor-neuron-like NSC-34 cells and transgenic mouse model of amyotrophic lateral sclerosis.

FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2009, Volume: 23, Issue:11

Novel therapeutic approaches for the treatment of neurodegenerative disorders comprise drug candidates designed specifically to act on multiple central nervous system targets. We have recently synthesized multifunctional, nontoxic, brain-permeable iron-chelating drugs, M30 and HLA20, possessing the N-propargylamine neuroprotective moiety of rasagiline (Azilect) and the iron-chelating moiety of VK28. The present study demonstrates that M30 and HLA20 possess a wide range of pharmacological activities in mouse NSC-34 motor neuron cells, including neuroprotective effects against hydrogen peroxide- and 3-morpholinosydnonimine-induced neurotoxicity, induction of differentiation, and up-regulation of hypoxia-inducible factor (HIF)-1alpha and HIF-target genes (enolase1 and vascular endothelial growth factor). Both compounds induced NSC-34 neuritogenesis, accompanied by a marked increase in the expression of brain-derived neurotrophic factor and growth-associated protein-43, which was inhibited by PD98059 and GF109203X, indicating the involvement of mitogen-activated protein kinase and protein kinase C pathways. A major finding was the ability of M30 to significantly extend the survival of G93A-SOD1 amyotrophic lateral sclerosis mice and delay the onset of the disease. These properties of the novel multimodal iron-chelating drugs possessing neuroprotective/neuritogenic activities may offer future therapeutic possibilities for motor neurodegenerative diseases.

Topics: Amyotrophic Lateral Sclerosis; Animals; Apoptosis; Brain-Derived Neurotrophic Factor; Cell Differentiation; Cell Line; Disease Models, Animal; Extracellular Signal-Regulated MAP Kinases; GAP-43 Protein; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hydrogen Peroxide; Hydroxyquinolines; Hypoxia-Inducible Factor 1, alpha Subunit; Iron Chelating Agents; Mice; Mice, Transgenic; Molsidomine; Motor Neurons; Neurites; Neuroprotective Agents; Phosphopyruvate Hydratase; Piperazines; Proto-Oncogene Proteins c-akt; Receptors, Transferrin; Signal Transduction; Superoxide Dismutase; Superoxide Dismutase-1; Vascular Endothelial Growth Factor A

2009