Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents

Martino, Maria Vittoria; Guandalini, Luca; Mannelli, Lorenzo Di Cesare; Menicatti, Marta; Bartolucci, Gianluca; Dei, Silvia; Manetti, Dina; Teodori, Elisabetta; Ghelardini, Carla; Romanelli, Maria Novella

doi:10.1016/j.bmc.2017.02.019

Cited by 8 publications

(4 citation statements)

References 17 publications

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“…The degradation plots of KEE and Enalapril showed an important decay rate, and their calculated half-life ( t 1/2 values 95 min. and 22 min respectively), comparable to what reported in the literature 32 , 33 , demonstrate that the employed human and rat plasma batches were enzymatically active ( Supplemental material SF9–SF10 ). Conversely, the studied compounds did not exhibit significant degradation in all matrices tested so far.…”

Section: Resultssupporting

confidence: 86%

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Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry

Menicatti

Pallecchi

Bua

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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Rheumatoid arthritis (RA) is a chronic inflammatory disease caused by a faulty autoimmune response. Recently, it was reported that some human carbonic anhydrases (CAs) isoforms are overexpressed in inflamed synovium of RA patients. New CA inhibitors (CAIs) incorporating CA-binding moiety and the cyclooxygenase inhibitor tail (nonsteroidal anti-inflammatory drug [NSAID] type) were studied. The aim of this work is the evaluation of the chemical stability of NSAID − CAI hybrids towards spontaneous or enzymatic hydrolysis by LC-MS/MS. The analytes are isomer pairs of 6- or 7-hydroxycoumarin, their different fragment ions abundances allowed the development of a mathematical tool (LEDA) to distinguish them. LEDA reliability at ng mL−1 level was checked (>90%), being proved the effectiveness in the correct assignment of the isomer present in the sample. The hybrids resulted stable in all tested matrices allowing us to conclude that these compounds reach the target tissues unmodified, opening perspectives for their development in the treatment of inflammation.

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Section: Resultssupporting

confidence: 86%

“…In order to establish the hydrolytic activity of the employed plasma batches, two reference compounds were tested, following the procedure reported in the section ‘Validation of LC-MS/MS methods’: KEE (half-life <2 h) and enalapril (half-life <0.5 h) to verify the human and rat plasma activity, respectively 32 , 33 .…”

Section: Resultsmentioning

confidence: 99%

Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry

Menicatti

Pallecchi

Bua

et al. 2018

Journal of Enzyme Inhibition and Medicinal Chemistry

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“…unifiram [DM 232] and sunifiram [DM 235]), which are now popular on the web. Together with sapunifiram (MN19 [81]), these may constitute novel anti-amnesic compounds structurally related to ampakines [82,83].…”

Section: Racetams Including Piracetammentioning

confidence: 99%

Benefits and Harms of ‘Smart Drugs’ (Nootropics) in Healthy Individuals

Schifano

Catalani

Sharif

et al. 2022

Drugs

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Smart drugs' (also known as 'nootropics ' and 'cognitive enhancers' [CEs]) are being used by healthy subjects (i.e. students and workers) typically to improve memory, attention, learning, executive functions and vigilance, hence the reference to a 'pharmaceutical cognitive doping behaviour'. Whilst the efficacy of known CEs in individuals with memory or learning deficits is well known, their effect on non-impaired brains is still to be fully assessed. This paper aims to provide an overview on the prevalence of use; putative neuroenhancement benefits and possible harms relating to the intake of the most popular CEs (e.g. amphetamine-type stimulants, methylphenidate, donepezil, selegiline, modafinil piracetam, benzodiazepine inverse agonists, and unifiram analogues) in healthy individuals. CEs are generally perceived by the users as effective, with related enthusiastic anecdotal reports. However, their efficacy in healthy individuals is uncertain and any reported improvement temporary. Conversely, since most CEs are stimulants, the related modulation of central noradrenaline, glutamate, and dopamine levels may lead to cardiovascular, neurological and psychopathological complications. Furthermore, CEs' use can be associated with paradoxical short-and long-term cognitive decline; decreased potential for plastic learning; and addictive behaviour. Finally, the non-medical use of any potent psychotropic raises serious ethical and legal issues, with nootropics having the potential to become a major public health concern. Further studies investigating CE-associated social, psychological, and biological outcomes are urgently needed to allow firm conclusions to be drawn on the appropriateness of CE use in healthy individuals. Key points• Cognitive enhancers (CEs) are extensively and increasingly being used by healthy active subjects, with student use having been reported in the range of 1.3-33% across studies, with variations depending on country and definition of cognitive doping. However, their efficacy on non-impaired brains is uncertain and any reported improvement is temporary. • Conversely, since most CEs are stimulants, the modulation of central neurotransmitter pathways could lead to severe complications and can be associated with paradoxical short-and long-term cognitive decline; decreased potential for plastic learning; and addictive behaviour. • Finally, non-medical use of CEs raises serious ethical and legal issues, and CEs have the potential to become a major public health concern

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“…Although some lead compounds have undefined mechanisms, most compounds exhibit excellent bioactivity. Significantly, the bioactivity depends not only on the molecular integrity, but also on interconnected functional groups (Han et al., 2020; Huang et al., 2020; Mao et al., 2016; Martino et al., 2017; Schnider et al., 2020). Thus, the modifiability and findability of the active site should be the standard development of lead compounds.…”

Section: Introductionmentioning

confidence: 99%

Quinoline, with the active site of 8‐hydroxyl, efficiently inhibits Micropterus salmoides rhabdovirus (MSRV) infection in vitro and in vivo

Yang

Zhang

et al. 2022

Journal of Fish Diseases

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Micropterus salmoides rhabdovirus (MSRV) is an significant pathogen that causes high mortality and related economic losses in bass aquaculture. There is no effective or approved therapy to date. In this study, we evaluated the anti-MSRV effects of 22 quinoline derivatives in grass carp ovary (GCO) cells. Among these compounds, 8-hydroxyquinoline exhibited valid inhibition in decreasing MSRV nucleoprotein gene expression levels of 99.3% with a half-maximal inhibitory concentrations (IC 50 ) value of 4.66 μM at 48 h. Moreover, 8-hydroxyquinoline significantly enhanced a protective effect in GCO cells by reducing the cytopathic effect (CPE). By comparing the anti-MSRV activity of 22 quinoline derivatives, we found that 8-hydroxyquinoline possessed the efficient active site of 8-hydroxyl and inhibited MSRV infection in vitro.For in vivo studies, 8-hydroxyquinoline via intraperitoneal injection exhibited an antiviral effect in MSRV-infected largemouth bass by substantially enhancing the survival rate by 15.0%. Importantly, the viral loads in the infected largemouth bass notably reduced in the spleen on the third days post-infection. Overall, 8-hydroxyquinoline was considered to be an efficient agent against MSRV in aquaculture.

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Piperazines as nootropic agents: New derivatives of the potent cognition-enhancer DM235 carrying hydrophilic substituents

Cited by 8 publications

References 17 publications

Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry

Resolution of co-eluting isomers of anti-inflammatory drugs conjugated to carbonic anhydrase inhibitors from plasma in liquid chromatography by energy-resolved tandem mass spectrometry

Benefits and Harms of ‘Smart Drugs’ (Nootropics) in Healthy Individuals

Quinoline, with the active site of 8‐hydroxyl, efficiently inhibits Micropterus salmoides rhabdovirus (MSRV) infection in vitro and in vivo

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