Polyamines and the NMDA receptor: Modifying intrinsic activities with aromatic substituents

Berger, Michael L.; Bitar, Abdallah Y.; Waitner, Matthew J.; Rebernik, Patrick; O’Sullivan, Mary C.

doi:10.1016/j.bmcl.2006.03.015

Cited by 11 publications

(4 citation statements)

References 18 publications

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“…Although stimulation of the NR by polyamines exhibits parallels to stimulation by increased pH, not only GluN1/2B, but also GluN1/2A and GluN1/2D combinations are subject to proton inhibition. 46 Systematic examination of mutated receptors did not result in correlations between spermine and proton sensitivities, 18 and also in our own studies, 42,47 inhibition by similar dicationic compound families was differently influenced by spermine and pH. Thus, stimulation by polyamines seems to depend on the pattern of specific acidic amino acid residues on the domain surfaces, rather than on the general neutralization of a local acidic milieu.…”

Section: Resultssupporting

confidence: 56%

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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Section: Resultssupporting

confidence: 56%

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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“…More precisely, pentamidine analogues were shown to interact with the spermine ligand binding site of this receptor channel complex [24], acting via a mechanism referred to as an inverse agonistic activity [25,26]. This is for instance the case of polyamines flanked with aromatic substituents that provide compounds with a more potent blocker activity towards NMDA receptor calcium channel complex [26]. In addition to these works, our data report in vivo efficiency of this class of compounds (arylamidines) towards the NMDA receptor.…”

Section: Discussionmentioning

confidence: 99%

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

Maurois

Pagès

et al. 2010

European Journal of Medicinal Chemistry

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“…Steroid-polyamine conjugates have variety of biological activities including antimicrobial activity (Shu et al, 2002) and DNA delivery property (Fujiwara et al, 2000). Polyamine derivatives with aromatic (Berger et al, 2006) and dansyl and related sulfonamides (Seiler et al, 1998) exhibited inhibition of specific binding of the NMDA channel blocker. Polyamine-porphyrin and polyamine-chlorine conjugates were used as photosensitizers for photodynamic therapy of cancers.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of bis, tris and tetra(dihydrocaffeoyl)polyamine conjugates as antibacterial agents against VRSA

et al. 2008

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Bis, tris and tetra(dihydrocaffeoyl)polyamine conjugates were synthesized using solid phase synthesis technique. These compounds were screened for antibacterial activity against methicillin-resistant Staphylococcus aureus (MRSA) (11 strains) and vancomycin-resistant S. aureus (VRSA) (4 strains). Bis, tris and tetra(dihydrocaffeoyl)polyamine analogues showed antibacterial activity against VRSA which were better than the reference drugs, vancomycin. Tetra(dihydrocaffeoyl)polyamine conjugate exhibited the highest activity. These compounds showed no cytotoxicity against vero cells.

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Polyamines and the NMDA receptor: Modifying intrinsic activities with aromatic substituents

Cited by 11 publications

References 18 publications

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

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

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

Synthesis of bis, tris and tetra(dihydrocaffeoyl)polyamine conjugates as antibacterial agents against VRSA

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