8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

Knez, Damijan; Diez‐Iriepa, Daniel; Chioua, Mourad; Gottinger, Andrea; Denic, Milica; Chantegreil, Fabien; Nachon, Florian; Brazzolotto, Xavier; Skrzypczak-Wiercioch, Anna; Meden, Anže; Pišlar, Anja; Kos, Janko; Žakelj, Simon; Stojan, Jure; Sałat, Kinga; Serrano, Julia; Fernández, Ana Patricia; Sánchez-García, Aitana; Martı́nez-Murillo, Ricardo; Binda, Claudia; López‐Muñoz, Francisco; Gobec, Stanislav; Marco‐Contelles, José

doi:10.1016/j.apsb.2023.01.013

Cited by 18 publications

(7 citation statements)

References 103 publications

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“…QNs 1 – 6 were prepared following methods previously described in our laboratory, and were identified and characterized using the appropriate analytical and spectroscopic data 6 .…”

Section: Methodsmentioning

confidence: 99%

“…1 ) as a potent inhibitor of human butyrylcholinesterase (hBChE) (IC 50 = 1.06 ± 0.31 nM) and human monoamine oxidase B (hMAO-B) (IC 50 = 4.46 ± 0.18 µM), which acts as a free radical-scavenger and biometal chelator that is permeable to the blood–brain-barrier (BBB). This compound was not cytotoxic and showed neuroprotective properties in the 6-hydroxydopamine-induced cell model of Parkinson’s disease 6 . Finally, in vivo studies demonstrated that QN6 showed anti-amnesic effects in the scopolamine-induced mouse model of AD without adverse effects on motor function and coordination 6 .…”

Section: Introductionmentioning

confidence: 94%

“…This compound was not cytotoxic and showed neuroprotective properties in the 6-hydroxydopamine-induced cell model of Parkinson’s disease 6 . Finally, in vivo studies demonstrated that QN6 showed anti-amnesic effects in the scopolamine-induced mouse model of AD without adverse effects on motor function and coordination 6 . To sum up, these results allowed us to identify QN6 as a promising candidate for the therapy of VD.…”

Section: Introductionmentioning

confidence: 94%

“…In this context, we have recently designed and synthesized new quinolylnitrones ( QNs ) 1 – 6 (Fig. 1 ) as potential therapeutic antioxidants agents for VD 6 . QNs 1 – 4 (Fig.…”

Section: Introductionmentioning

confidence: 99%

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Neuroprotective and antioxidant properties of new quinolylnitrones in in vitro and in vivo cerebral ischemia models

Chamorro

Izquierdo-Bermejo

Serrano

et al. 2023

Sci Rep

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Cerebral ischemia is a condition affecting an increasing number of people worldwide, and the main cause of disability. Current research focuses on the search for neuroprotective drugs for its treatment, based on the molecular targets involved in the ischemic cascade. Nitrones are potent antioxidant molecules that can reduce oxidative stress. Here we report the neuroprotective properties and the antioxidant power of the six new quinolylnitrones (QNs) 1–6 for their potential application in stroke therapy. QNs 1–4 are 2-chloro-8-hydroxy-substituted QNs bearing N-t-butyl or N-benzyl substituents at the nitrone motif located at C3, whereas QN5 and QN6 are 8-hydroxy QNs bearing N-t-butyl or N-benzyl substituents at the nitrone motif located at C2, respectively. In vitro neuroprotection studies using QNs 1–6 in an oxygen-glucose-deprivation model of cerebral ischemia, in human neuroblastoma cell cultures, indicate that all QNs have promising neuroprotective, anti-necrotic, anti-apoptotic, and anti-oxidant properties against experimental ischemia–reperfusion in neuronal cultures. QN6 stands out as the most balanced nitrone out of all tested QNs, as it strongly prevents decreased neuronal metabolic activity (EC50 = 3.97 ± 0.78 μM), as well as necrotic (EC50 = 3.79 ± 0.83 μM) and apoptotic cell death (EC50 = 3.99 ± 0.21 μM). QN6 showed high capacity to decrease superoxide production (EC50 = 3.94 ± 0.76 μM), similar to its parent molecule α-phenyl-tert-butyl nitrone (PBN) and the well-known anti-oxidant molecule N-acetyl-l-cysteine (NAC). Thus, QN6 demonstrated the highest antioxidant power out of the other tested QNs. Finally, in vivo treatment with QN6 in an experimental permanent stroke model elicited a significant reduction (75.21 ± 5.31%) of the volume size of brain lesion. Overall, QN6 is a potential agent for the therapy of cerebral ischemia that should be further investigated.

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“…QNs 1 – 6 were prepared following methods previously described in our laboratory, and were identified and characterized using the appropriate analytical and spectroscopic data 6 .…”

Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 94%

Section: Introductionmentioning

confidence: 94%

“…In this context, we have recently designed and synthesized new quinolylnitrones ( QNs ) 1 – 6 (Fig. 1 ) as potential therapeutic antioxidants agents for VD 6 . QNs 1 – 4 (Fig.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Neuroprotective and antioxidant properties of new quinolylnitrones in in vitro and in vivo cerebral ischemia models

Chamorro

Izquierdo-Bermejo

Serrano

et al. 2023

Sci Rep

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“…27 The presence of hydrazide-hydrazone linkers have also shown anti-cancer activity against non-small cell lung cancer cell lines (NSCLC's). [28][29][30] Quinolines are well known for their antimalarial nature and recently their uses have extended further into the disciplines of anti-diabetic agents, 31 anti-cancer therapeutics, 32,33 neurodegenerative diseases 34 etc. The quinoline base exhibits strong binding with various apoptotic proteins, thereby making the heterocycle a good starting point for anti-cancer drug design strategies.…”

Section: Introductionmentioning

confidence: 99%

Anti-proliferative activity of nitroquinolone fused acylhydrazones as non-small cell human lung cancer agents

et al. 2023

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Unveiling piperazine-quinoline hybrids as potential multi-target directed anti-Alzheimer’s agents: design, synthesis and biological evaluation

Nagani,

Shah,

Patel

et al. 2024

Mol Divers

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8-Hydroxyquinolylnitrones as multifunctional ligands for the therapy of neurodegenerative diseases

Cited by 18 publications

References 103 publications

Neuroprotective and antioxidant properties of new quinolylnitrones in in vitro and in vivo cerebral ischemia models

Neuroprotective and antioxidant properties of new quinolylnitrones in in vitro and in vivo cerebral ischemia models

Anti-proliferative activity of nitroquinolone fused acylhydrazones as non-small cell human lung cancer agents

Unveiling piperazine-quinoline hybrids as potential multi-target directed anti-Alzheimer’s agents: design, synthesis and biological evaluation

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