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Pregled bibliografske jedinice broj: 16278

Quinuclidinium-imidazolium compounds : synthesis, mode of interaction with acetylcholinesterase and effect upon Soman intoxicated mice


Simeon-Rudolf, Vera; Reiner, Elsa; Škrinjarić-Špoljar, Mira; Radić, Božica; Lucić, Ana; Primožič, Ines; Tomić, Srđanka
Quinuclidinium-imidazolium compounds : synthesis, mode of interaction with acetylcholinesterase and effect upon Soman intoxicated mice // Archives of toxicology, 72 (1998), 289-295 (međunarodna recenzija, članak, znanstveni)


Naslov
Quinuclidinium-imidazolium compounds : synthesis, mode of interaction with acetylcholinesterase and effect upon Soman intoxicated mice

Autori
Simeon-Rudolf, Vera ; Reiner, Elsa ; Škrinjarić-Špoljar, Mira ; Radić, Božica ; Lucić, Ana ; Primožič, Ines ; Tomić, Srđanka

Izvornik
Archives of toxicology (0340-5761) 72 (1998); 289-295

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
Acetylcholinesterase; Quinuclidine-imidazolium compounds; Reversible inhibition and protection of acetylcholinesterase agains phosphorylation; Antidotal effect against Soman poisoned mice; Soman

Sažetak
Four compounds were prepared: 3-oxo-1-methylquinuclidinium iodide (I), 2-hydroxyiminomethyl-1,3-dimethylimidazolium iodide (II) and two conjugates of I and II linked by -(CH2)3- (III) and -CH2-O-CH2- (IV). The aim was to evaluate separately the properties of I and II as opposed to III and IV, which contain both moieties in the same molecule. All four compounds were reversible inhibitors of acetylcholinesterase (AChE; EC 3.1.1.7). The enzyme/inhibitor dissocoation constants for the catalytic site ranged from 0.073 mM (II) to 1.6 mM (I). The dissociation constant of I for the allosteric (substrate inhibition) site was 4.8 mM. Possible binding of thge other compounds to the allosteric site could not be measured because II, III and IV reacted with the substrate acetylthiocholine (ATCh) and at high ATCh concentrations the non-enzymic reaction interfered with the enzymic hydrolysis of ATCh. The rate constants for the non-enzymic ATCh hydrolysis were between 23 and 37l/mol per min. All four compounds protected AChE against phosphorylation by Soman and VX. The protective index (PI) of I (calculated from binding of I to both, catalutic and allosteric sites in AChE) agreed with the measured PI; this confirms that allosteric binding contributes to the decrease of phosphorylation rates. The PI values obtained with III and IV were higher that those predicted by the assumption of their bindinbg to the AChE catalytic site only. The toxicity (i.p. LD50) of compounds I, II, III and IV for mice was 0.21, 0.68, 0.49 and 0.77 mmol/kg body wt. respectively. All four compounds protected mice against Soman when given (i.p.) together with atropine one min after Soman (s.C.). One-quarter of the LD_50 dose fully protected mice (survival of all animals) against 2.52 (IV), 2.00 (I and III) and 1.58 (II) LD_50 doses of Soman.

Izvorni jezik
Engleski

Znanstvena područja
Kemija



POVEZANOST RADA


Projekt / tema
00220104
00220105
119401

Ustanove
Institut za medicinska istraživanja i medicinu rada, Zagreb,
Prirodoslovno-matematički fakultet, Zagreb

Časopis indeksira:


  • Current Contents Connect (CCC)
  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus
  • MEDLINE


Uključenost u ostale bibliografske baze podataka:


  • Index medicus
  • Toxline