2019
DOI: 10.1038/s41598-019-41272-4
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Conjugates of methylene blue with γ-carboline derivatives as new multifunctional agents for the treatment of neurodegenerative diseases

Abstract: We studied the inhibitory activity of methylene blue (MB) γ-carbolines (gC) conjugates (MB-gCs) against human erythrocyte acetylcholinesterase (AChE), equine serum butyrylcholinesterase (BChE), and a structurally related enzyme, porcine liver carboxylesterase (CaE). In addition, we determined the ability of MB-gCs to bind to the peripheral anionic site (PAS) of Electrophorus electricus AChE (EeAChE) and competitively displace propidium iodide from this site. Moreover, we examined the ability of MB-gCs to scave… Show more

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Cited by 26 publications
(18 citation statements)
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References 104 publications
(115 reference statements)
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“…Beyond quinone structures, there are many other aromatic molecules that can provide themselves not only redox activity but also lipophilic properties to cross the membrane. For instance, the phenothiazine ring allows Methylene Blue both to reach the mitochondrial matrix and to perform redox reactions reducing ROS formation [165,166]; indeed, this activity is ensured in vivo, increasing attentional functions and preserving dopaminergic neurons in a PD rat model [157,167]. In Szeto-Schiller tetrapeptides the tyrosine or dimethyl tyrosine residues can scavenge ROS but, differently from the previous drugs, they act in the IMM without joining the mitochondrial matrix, as described by Rocha et al [168]; both in in vitro and in vivo studies they have shown multiple functions deriving from the antioxidant activity, making it a promising compound for AD therapy [139], but they have also provided interesting results in further studies on ALS cell models and in PD and ALS mice, ensuring increased survival and motor performance enhancement due to neuroprotective effects [169].…”
Section: Synthetic Antioxidantsmentioning
confidence: 99%
“…Beyond quinone structures, there are many other aromatic molecules that can provide themselves not only redox activity but also lipophilic properties to cross the membrane. For instance, the phenothiazine ring allows Methylene Blue both to reach the mitochondrial matrix and to perform redox reactions reducing ROS formation [165,166]; indeed, this activity is ensured in vivo, increasing attentional functions and preserving dopaminergic neurons in a PD rat model [157,167]. In Szeto-Schiller tetrapeptides the tyrosine or dimethyl tyrosine residues can scavenge ROS but, differently from the previous drugs, they act in the IMM without joining the mitochondrial matrix, as described by Rocha et al [168]; both in in vitro and in vivo studies they have shown multiple functions deriving from the antioxidant activity, making it a promising compound for AD therapy [139], but they have also provided interesting results in further studies on ALS cell models and in PD and ALS mice, ensuring increased survival and motor performance enhancement due to neuroprotective effects [169].…”
Section: Synthetic Antioxidantsmentioning
confidence: 99%
“…[ 297 ] Bachurin et al examined the potential of methylene blue and γ‐carboline derivatives conjugates as a new multifunctional treatment of NDs; both compounds are neuroprotectant, target distinct pathological pathways, and exhibit significant synergistic antioxidant action. [ 298 ] More details on additional cases of multifunctional therapeutic NPs can be seen in Table 8 .…”
Section: Multifunctional Stimuli‐responsive and Site‐directed Nanopmentioning
confidence: 99%
“…Using MB as a pharmacophore for the design of multitarget drugs, MB conjugates with γ‐carboline derivatives as parts of the Dimebon molecule (Figure 1) were prepared 50,51 . Dimebon successfully passed phase II clinical trials, but, like many other drugs subjected to clinical trials for the treatment of AD, did not show statistically significant efficacy in comparison with placebo 52,53 .…”
Section: Stimulation Of Cellular Bioenergeticmentioning
confidence: 99%