1,2-Ethane bis-1-amino-4-benzamidine is active against several brain insult and seizure challenges through anti-NMDA mechanisms targeting the 3H-TCP binding site and antioxidant action

Vamecq, Jòseph; Maurois, Pierre; Pagès, Nicole; Bac, Pierre; Stables, James P.; Gressèns, Pierre; Stanicki, Dimitri; Eynde, Jean Jacques Vanden

doi:10.1016/j.ejmech.2010.03.044

Cited by 16 publications

(14 citation statements)

References 32 publications

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“…Identity and purity of novel compounds were in addition confirmed by HRMS (Waters QToF 2) and elemental analyses (Centre Wallon de Recherches Agronomiques, Libramont-Chevigny, Belgium or Laboratoire de Microanalyse Organique of the Institut des Sciences Appliquées de Rouen, France). Derivatives 2 [19], 3 [20], 4 [21], 6 [22], 8 [22], 10 [23], 11 [24], 12 [25], 13 [22], 14 [22], 15 [22], and 17 [26] have been described in the literature. Compound 16 was commercially available (Aldrich, St. Louis, MO, USA).…”

Section: Methodsmentioning

confidence: 99%

Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study

et al. 2013

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Some compounds articulated around a piperazine or an ethylenediamine linker have been evaluated in vitro to determine their activity in the presence of a 3T6 fibroblast cell line and an axenic culture of Pneumocystis carinii, respectively. The most efficient antifungal derivatives, namely N,N′-bis(benzamidine-4-yl)ethane-1,2-diamine (compound 6, a diamidine) and N-(benzamidine-4-yl)-N′-phenylethane-1,2-diamine (compound 7, a monoamidine), exhibited no cytotoxicity and were evaluated in vivo in a rat model. Only the diamidine 6 emerged as a promising hit for further studies.

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Section: Methodsmentioning

confidence: 99%

Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study

et al. 2013

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“…In this respect, experimental magnesium deficiency in mice has been shown to lower seizure threshold to N-methyl-D-aspartate (NMDA) [22] and to induce susceptibility to audiogenic seizures [23]. Magnesium deficiency-dependent audiogenic seizures (MDDAS) represent a useful murine experimental in vivo tool to identify a large spectrum of brain protective drugs and mechanisms including anti-inflammatory, anti-oxidant, neuroprotective and/or anti-epileptic compound properties [22–28]. The pro-convulsant status induced by magnesium deficiency may be the result of a loss of protective effects normally provided by magnesium.…”

Section: Introductionmentioning

confidence: 99%

Brain protection by rapeseed oil in magnesium-deficient mice

Pagès¹,

Maurois²,

Delplanque³

et al. 2011

Prostaglandins, Leukotrienes and Essential Fatty Acids

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Diets given for 30 days with various mono-(MUFA) and poly-(PUFA) unsaturated fatty acid contents were evaluated for brain protection in magnesium-deficient mice: a commercial and three synthetic diets (n-6PUFA, n-3PUFA and MUFA-based chows enriched with 5% corn/sunflower oils 1:3, with 5% rapeseed oil and with 5% high oleic acid sunflower oil/sunflower oil 7:3, respectively). Unlike magnesium deprivation, they induced significant differences in brain and erythrocyte membrane phospholipid fatty acid compositions. n-3PUFA but not other diets protected magnesium-deficient mice against hyperactivity and moderately towards maximal electroshock- and NMDA-induced seizures. This diet also inhibited audiogenic seizures by 50%, preventing animal deaths. Because, like n-6PUFA diet, matched control MUFA diet failed to induce brain protections, alpha-linolenate (ALA) rather than reduced n-6 PUFA diet content is concluded to cause n-3PUFA neuroprotection. Present in vivo data also corroborate literature in vitro inhibition of T type calcium channels by n-3 PUFA, adding basis to ALA supplementation in human anti-epileptic/neuroprotective strategies.

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“…The piperazine and homopiperazine derivatives are known compounds; 15,29,30 also several of the open chain analogs have been described; 31 40, 43 and 44 are described here for the first time and were prepared via the bisbenzonitriles in 3 steps. The first one was equivalent to step one in Scheme 1 (with DMF as the dry solvent).…”

Section: Synthesesmentioning

confidence: 99%

“…The obtained bisbenzonitriles were converted into the corresponding bisbenzamidines via the bisbenzamidoximes ( Procedure B ). 31 …”

Section: Synthesesmentioning

confidence: 99%

Pentamidine analogs as inhibitors of [3H]MK-801 and [3H]ifenprodil binding to rat brain NMDA receptors

Berger

Maciejewska

Eynde

et al. 2015

Bioorganic & Medicinal Chemistry

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The anti-protozoal drug pentamidine is active against opportunistic Pneumocystis pneumonia, but in addition has several other biological targets, including the NMDA receptor (NR). Here we describe the inhibitory potencies of 76 pentamidine analogs at 2 binding sites of the NR, the channel binding site labeled with [3H]MK-801 and the [3H]ifenprodil binding site. Most analogs acted weaker at the ifenprodil than at the channel site. The spermine-sensitivity of NR inhibition by the majority of the compounds was reminiscent of other long-chain dicationic NR blockers. The potency of the parent compound as NR blocker was increased by modifying the heteroatoms in the bridge connecting the 2 benzamidine moieties and also by integrating the bridge into a seven-membered ring. Docking of the 45 most spermine-sensitive bisbenzamidines to a recently described acidic interface between the N-terminal domains of GluN1 and GluN2B mediating polyamine stimulation of the NR revealed the domain contributed by GluN1 as the most relevant target.

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1,2-Ethane bis-1-amino-4-benzamidine is active against several brain insult and seizure challenges through anti-NMDA mechanisms targeting the 3H-TCP binding site and antioxidant action

Cited by 16 publications

References 32 publications

Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study

Diamidines versus Monoamidines as Anti-Pneumocystis Agents: An in Vivo Study

Brain protection by rapeseed oil in magnesium-deficient mice

Pentamidine analogs as inhibitors of [3H]MK-801 and [3H]ifenprodil binding to rat brain NMDA receptors

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