Synthesis and kinase inhibitory activity of novel substituted indigoids

Beauchard, Anne; Laborie, Hélène; Rouillard, Hervé; Lozach, Olivier; Ferandin, Yoan; Guével, Rémy Le; Guguen‐Guillouzo, Christiane; Meijer, Laurent; Besson, Thierry; Thiéry, Valérie

doi:10.1016/j.bmc.2009.07.051

Cited by 57 publications

(31 citation statements)

References 32 publications

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“…42,80,86 In 2009, Thieŕy and co-workers described the biological activity of various bis-indole indigoid analogues against five CMGC kinase family members reportedly involved in the promotion of Alzheimer's dementia (CDK1/5, 87 GSK3, 88 CK1, 89 DYRK1A). 90 Although some indigoids 22a−d (Table 7, Figure 12) exhibited moderate in vitro inhibition of DYRK1A, low selectivity and far better activity was observed versus other kinases implicated in Alzheimer's progression. However, it should be noted that, in the field of kinase inhibition, gaining selectivity among kinase targets with high Figure 10.…”

Section: Acs Chemical Neurosciencementioning

confidence: 99%

Recent Advances in the Design, Synthesis, and Biological Evaluation of Selective DYRK1A Inhibitors: A New Avenue for a Disease Modifying Treatment of Alzheimer’s?

Smith

Medda

Gokhale

et al. 2012

ACS Chem. Neurosci.

132

124

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Section: Acs Chemical Neurosciencementioning

confidence: 99%

Recent Advances in the Design, Synthesis, and Biological Evaluation of Selective DYRK1A Inhibitors: A New Avenue for a Disease Modifying Treatment of Alzheimer’s?

Smith

Medda

Gokhale

et al. 2012

ACS Chem. Neurosci.

132

124

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“…Several studies focused on the role of GSK-3β because, in addition to promoting tau hyperphosphorylation, high levels of GSK-3β activity lead to alterations in AβPP processing and increased neuronal death (181,(184)(185)(186). Approaches to therapeutically inhibit GSK-3β activity have mainly included the use of lithium chloride, and to a lesser extent, indigoids (181, 184-187).…”

Section: Targeting Tau Pathologymentioning

confidence: 99%

“…Approaches to therapeutically inhibit GSK-3β activity have mainly included the use of lithium chloride, and to a lesser extent, indigoids (181,(184)(185)(186)(187). In several uncontrolled or retrospective human studies, it was found that prior use of lithium therapy protected against dementia and was associated with better performance on cognitive tests (188)(189)(190)(191).…”

Section: Targeting Tau Pathologymentioning

confidence: 99%

“…The increased oxidative stress induced by the accumulation of misfolded, aggregated cytoskeletal proteins exacerbates insulin resistance and neuroinflammation. Therefore, treatment with chemical inhibitors of one or more ADrelevant kinases may reduce the rates of neurofibrillary pathology and help prevent progressive brain insulin resistance.Several studies focused on the role of GSK-3β because, in addition to promoting tau hyperphosphorylation, high levels of GSK-3β activity lead to alterations in AβPP processing and increased neuronal death (181,(184)(185)(186). Approaches to therapeutically inhibit GSK-3β activity have mainly included the use of lithium chloride, and to a lesser extent, indigoids (181, 184-187).…”

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Therapeutic targets of brain insulin resistance in sporadic Alzheimer s disease

Monte

2012

Front Biosci

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Growing evidence supports roles for brain insulin and insulin-like growth factor (IGF) resistance and metabolic dysfunction in the pathogenesis of Alzheimer's disease (AD). Whether the underlying problem stems from a primary disorder of central nervous system (CNS) neurons and glia, or secondary effects of systemic diseases such as obesity, Type 2 diabetes, or metabolic syndrome, the end-results include impaired glucose utilization, mitochondrial dysfunction, increased oxidative stress, neuroinflammation, and the propagation of cascades that result in the accumulation of neurotoxic misfolded, aggregated, and ubiquitinated fibrillar proteins. This article reviews the roles of impaired insulin and IGF signaling to AD-associated neuronal loss, synaptic disconnection, tau hyperphosphorylation, amyloid-beta accumulation, and impaired energy metabolism, and discusses therapeutic strategies and lifestyle approaches that could be used to prevent, delay the onset, or reduce the severity of AD. Finally, it is critical to recognize that AD is heterogeneous and has a clinical course that fully develops over a period of several decades. Therefore, early and multi-modal preventive and treatment approaches should be regarded as essential. KeywordsAmyloid; Anti-oxidants; Brain diabetes; Brain insulin resistance; Incretins; Insulin; Insulin sensitizers; Liver-Brain-Axis; Metal Chelation; Neuroprotection; Nitrosamine; Oxidative Stress; Polyphenols; Statins; Streptozotocin; Tau; Type 3 diabetes INTRODUCTIONThe gold standard for definitively diagnosing AD is to perform a postmortem examination of the brain, with the objective of demonstrating beyond-normal aging associated densities of neurofibrillary tangles, neuritic plaques, and amyloid-beta 40-42 kD fragments of amyloid beta precursor protein (AβPP-Aβ) deposits in corticolimbic structures, bearing in mind that neurodegeneration frequently involves multiple other cortical regions as well. The common thread among these characteristic lesions is that they harbor insoluble aggregates of abnormally phosphorylated and ubiquitinated tau, and neurotoxic AβPP-Aβ in the form of Send correspondence to: Suzanne M. de la Monte, Rhode Island Hospital, 55 Claverick Street, Room 419, Providence, RI. 02903, Tel: 401-444-7364, Fax: 401-444-2939, Suzanne_DeLaMonte_MD@Brown.edu. HHS Public Access Author manuscriptFront Biosci (Elite Ed). Author manuscript; available in PMC 2015 August 26. Published in final edited form as:Front Biosci (Elite Ed). ; 4: 1582-1605. Author Manuscript Author ManuscriptAuthor ManuscriptAuthor Manuscript oligomers, fibrillar aggregates, or extracellular plaques. Secreted AβPP-Aβ oligomers have been demonstrated to be neurotoxic and to inhibit hippocampal long-term potentiation, i.e. synaptic plasticity (1).To improve diagnosis and treatment, we must learn to connect the development and progression of neurodegeneration with molecular, biochemical, physiological, neuroimaging, and clinical abnormalities in AD. Several strategies could be taken to advance this proc...

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“…Since various kinases are involved in the growth of microorganisms and because many oxindoles are kinase inhibitors 6,[12][13][14][15][16] , a variety of 3-substituted indolin-2-ones have been utilized as anticancer drugs or drug candidates [17][18][19][20][21] . A representative member of this class is Sunitinib (SU11248, SutentTM; Pfizer, Cairo, Egypt) which is currently used in the clinics as a multi-targeting tyrosine kinase inhibitor with antiangiogenic activity Figure 1 22,23 .…”

Section: Introductionmentioning

confidence: 99%