Zrinka Kovarik

Summary

Affiliation: Institute for Medical Research and Occupational Health
Country: Croatia

Publications

  1. ncbi request reprint Interaction of pyridinium oximes with acetylcholinesterase and their effect on organophosphate-poisoned mice
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, POB 291, HR 10001 Zagreb, Croatia
    J Mol Neurosci 30:113-4. 2006
  2. pmc Centrally acting oximes in reactivation of tabun-phosphoramidated AChE
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, HR 10001 Zagreb, Croatia Electronic address
    Chem Biol Interact 203:77-80. 2013
  3. ncbi request reprint An improvement in segregation of human butyrylcholinesterase phenotypes having the fluoride-resistant variants
    Zrinka Kovarik
    Institute of Medical Research and Occupational Health, Zagreb, Croatia
    Arh Hig Rada Toksikol 54:239-44. 2003
  4. ncbi request reprint Interaction of human butyrylcholinesterase variants with bambuterol and terbutaline
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, POB 291, HR 10001 Zagreb, Croatia
    J Enzyme Inhib Med Chem 19:113-7. 2004
  5. ncbi request reprint Structure-activity approach in the reactivation of tabun-phosphorylated human acetylcholinesterase with bispyridinium para-aldoximes
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR 10000 Zagreb, Croatia
    Arh Hig Rada Toksikol 58:201-9. 2007
  6. ncbi request reprint Pretreatment with pyridinium oximes improves antidotal therapy against tabun poisoning
    Ana Lucić Vrdoljak
    Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia
    Toxicology 228:41-50. 2006
  7. ncbi request reprint A conjugate of pyridine-4-aldoxime and atropine as a potential antidote against organophosphorus compounds poisoning
    Jasna Lovrić
    University of Zagreb, School of Medicine, Zagreb, Croatia
    Acta Biochim Pol 58:193-8. 2011
  8. doi request reprint Oximes: Reactivators of phosphorylated acetylcholinesterase and antidotes in therapy against tabun poisoning
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia
    Chem Biol Interact 175:173-9. 2008
  9. doi request reprint Pseudo-catalytic scavenging: searching for a suitable reactivator of phosphorylated butyrylcholinesterase
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, POB 291, HR 10001 Zagreb, Croatia
    Chem Biol Interact 187:167-71. 2010
  10. doi request reprint In vivo experimental approach to treatment against tabun poisoning
    Suzana Berend
    Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia
    J Enzyme Inhib Med Chem 25:531-6. 2010

Collaborators

Detail Information

Publications34

  1. ncbi request reprint Interaction of pyridinium oximes with acetylcholinesterase and their effect on organophosphate-poisoned mice
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, POB 291, HR 10001 Zagreb, Croatia
    J Mol Neurosci 30:113-4. 2006
    ..We investigated the interactions of five bispyridinium oximes with human erythrocyte AChE and their effects on tabun- and soman-poisoned mice...
  2. pmc Centrally acting oximes in reactivation of tabun-phosphoramidated AChE
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, HR 10001 Zagreb, Croatia Electronic address
    Chem Biol Interact 203:77-80. 2013
    ..The phosphoramidated-hAChE choline-binding site mutant Y337A showed three-times enhanced reactivation capacity with non-triazole imidazole containing aldoximes (RS113B, RS113A and RS115A) and acetamide derivative (RS194B) than with 2PAM...
  3. ncbi request reprint An improvement in segregation of human butyrylcholinesterase phenotypes having the fluoride-resistant variants
    Zrinka Kovarik
    Institute of Medical Research and Occupational Health, Zagreb, Croatia
    Arh Hig Rada Toksikol 54:239-44. 2003
    ..Hence, determination of the residual activity after 30 min inhibition is recommended for the segregation of the suxamethonium sensitive fluoride-resistant variants...
  4. ncbi request reprint Interaction of human butyrylcholinesterase variants with bambuterol and terbutaline
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, POB 291, HR 10001 Zagreb, Croatia
    J Enzyme Inhib Med Chem 19:113-7. 2004
    ..The affinity of all studied BChE variants for terbutaline was low, which suggests that terbutaline originating from bambuterol hydrolysis should not affect the hydrolysis of bambuterol by BChE...
  5. ncbi request reprint Structure-activity approach in the reactivation of tabun-phosphorylated human acetylcholinesterase with bispyridinium para-aldoximes
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR 10000 Zagreb, Croatia
    Arh Hig Rada Toksikol 58:201-9. 2007
    ..Since aldoximes are also reversible inhibitors of native acetylcholinesterase, we determined dissociation constants and their protective index against acetylcholinesterase inactivation by tabun...
  6. ncbi request reprint Pretreatment with pyridinium oximes improves antidotal therapy against tabun poisoning
    Ana Lucić Vrdoljak
    Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia
    Toxicology 228:41-50. 2006
    ....
  7. ncbi request reprint A conjugate of pyridine-4-aldoxime and atropine as a potential antidote against organophosphorus compounds poisoning
    Jasna Lovrić
    University of Zagreb, School of Medicine, Zagreb, Croatia
    Acta Biochim Pol 58:193-8. 2011
    ..It appears that ATR-4-OX has a therapeutic effect related to the reactivation of phosphylated AChE, but not to receptor antagonization...
  8. doi request reprint Oximes: Reactivators of phosphorylated acetylcholinesterase and antidotes in therapy against tabun poisoning
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia
    Chem Biol Interact 175:173-9. 2008
    ..Since the reactivating efficacy of the oximes in vitro corresponded to their therapeutic efficacy in vivo, it seems that pharmacological effect of these oximes is indeed primarily related to the reactivation of tabun-phosphorylated AChE...
  9. doi request reprint Pseudo-catalytic scavenging: searching for a suitable reactivator of phosphorylated butyrylcholinesterase
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, POB 291, HR 10001 Zagreb, Croatia
    Chem Biol Interact 187:167-71. 2010
    ..Using molecular mechanics, we performed docking of the oximes to tabun-inhibited BChE in order to discuss possible structural modifications of bispyridinium oximes to improve reactivation of phosphorylated BChE...
  10. doi request reprint In vivo experimental approach to treatment against tabun poisoning
    Suzana Berend
    Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia
    J Enzyme Inhib Med Chem 25:531-6. 2010
    ..K048 is our oxime of choice for future research, as it shows better protective and reactivating potency...
  11. ncbi request reprint In vitro and in vivo evaluation of pyridinium oximes: mode of interaction with acetylcholinesterase, effect on tabun- and soman-poisoned mice and their cytotoxicity
    Maja Calić
    Institute for Medical Research and Occupational Health, Ksaverska c 2, P O Box 291, HR 10001 Zagreb, Croatia
    Toxicology 219:85-96. 2006
    ..The combination of HI-6 and atropine is the therapy of choice for soman poisoning...
  12. doi request reprint Evaluation of oxime k203 as antidote in tabun poisoning
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, Zagreb, Croatia
    Arh Hig Rada Toksikol 60:19-26. 2009
    ..This therapeutic improvement obtained by K203 in tabun-poisoning places this oxime in the spotlight for further development...
  13. ncbi request reprint Evaluation of monoquaternary pyridinium oximes potency to reactivate tabun-inhibited human acetylcholinesterase
    Renata Odzak
    Department of Chemistry, Faculty of Science, University of Zagreb, Horvatovac 102a, HR 10000 Zagreb, Croatia
    Toxicology 233:85-96. 2007
    ....
  14. doi request reprint Amino acid residues involved in stereoselective inhibition of cholinesterases with bambuterol
    Anita Bosak
    Institute for Medical Research and Occupational Health, Ksaverska c 2, P O Box 291, HR 10001 Zagreb, Croatia
    Arch Biochem Biophys 471:72-6. 2008
    ..Peripheral site mutations (Y124Q and Y72N/Y124Q/Y337A) increased inhibition rate by S- more than R-bambuterol and consequently diminished the stereoselectivity...
  15. doi request reprint Peripheral site and acyl pocket define selective inhibition of mouse butyrylcholinesterase by two biscarbamates
    Anita Bosak
    Institute for Medical Research and Occupational Health, POB 291, HR 10000 Zagreb, Croatia
    Arch Biochem Biophys 529:140-5. 2013
    ..Interestingly, the residues that define selective inhibition of mouse BChE by biscarbamates also affect the stereoselectivity of enzymes...
  16. doi request reprint Interactions of pyridinium oximes with acetylcholinesterase
    Goran Sinko
    Institute for Medical Research and Occupational Health, P O Box 291, HR 10001 Zagreb, Croatia
    Chem Biol Interact 187:172-6. 2010
    ....
  17. doi request reprint Interactions of butane, but-2-ene or xylene-like linked bispyridinium para-aldoximes with native and tabun-inhibited human cholinesterases
    Maja Calić
    Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia
    Chem Biol Interact 175:305-8. 2008
    ..However, lower BChE affinities for K074 and K075 compared to AChE suggest that the fast tabun-inhibited AChE reactivation by these compounds would not be obstructed by their interactions with BChE in vivo...
  18. ncbi request reprint Active site mutant acetylcholinesterase interactions with 2-PAM, HI-6, and DDVP
    Zrinka Kovarik
    Institute for Medical Research and Occupational Health, Ksaverska c 2, POB 291, HR 10001 Zagreb, Croatia
    Biochem Biophys Res Commun 342:973-8. 2006
    ..A high extent of oxime-assisted reactivation of all conjugates was achieved, but rates by both oximes were up to 10 times slower for phosphorylated mutants than for AChE w.t...
  19. doi request reprint The cholinergic and non-cholinergic effects of organophosphates and oximes in cultured human myoblasts
    Maja Katalinić
    Institute for Medical Research and Occupational Health, Zagreb, Croatia
    Chem Biol Interact 203:144-8. 2013
    ..Overall, the effects of OPs and oximes demonstrated here might play an important role in muscle regeneration which importantly determines the final outcome of OP myotoxicity...
  20. ncbi request reprint Structure-inhibition relationships in the interaction of butyrylcholinesterase with bambuterol, haloxon and their leaving groups
    Goran Sinko
    Institute for Medical Research and Occupational Health, Ksaverska cesta 2, POB 291, HR 10001 Zagreb, Croatia
    Chem Biol Interact 157:421-3. 2005
  21. doi request reprint Metaproterenol, isoproterenol, and their bisdimethylcarbamate derivatives as human cholinesterase inhibitors
    Anita Bosak
    Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR 10000 Zagreb, Croatia
    J Med Chem 55:6716-23. 2012
    ..All studied cholinesterases displayed poor affinity for metaproterenol and isoproterenol, yet BChE(UU) had an affinity about five times higher than that of AChE...
  22. doi request reprint Structural aspects of flavonoids as inhibitors of human butyrylcholinesterase
    Maja Katalinić
    Institute for Medical Research and Occupational Health, Ksaverska cesta 2, HR 10000 Zagreb, Croatia
    Eur J Med Chem 45:186-92. 2010
    ..Cytotoxicity was observed only for fisetin, apigenin and luteolin in the THP-1 cell line with IC50 of 30, 60 and 70 micromol/L, respectively...
  23. doi request reprint Mechanism of stereoselective interaction between butyrylcholinesterase and ethopropazine enantiomers
    Goran Sinko
    Institute for Medical Research and Occupational Health, POB 291, HR 10001 Zagreb, Croatia
    Biochimie 93:1797-807. 2011
    ..The respective dissociation constants for the complexes between acetylated BChE and ethopropazine were 268, 730 and 365 nM. Butyrylcholinesterase had higher affinity for R-ethopropazine...
  24. doi request reprint Stereoselective inhibition of human, mouse, and horse cholinesterases by bambuterol enantiomers
    Anita Bosak
    Institute for Medical Research and Occupational Health, Ksaverska c 2, Zagreb, Croatia
    Chem Biol Interact 175:192-5. 2008
    ..Since BChE inhibition by bambuterol enantiomers was at least 8000 times faster than that of AChE, both bambuterol enantiomers proved to be selective BChE inhibitors, as was previously shown for racemate...
  25. ncbi request reprint Limitation of the Ellman method: cholinesterase activity measurement in the presence of oximes
    Goran Sinko
    Institute for Medical Research and Occupational Health, HR 10001 Zagreb, Croatia
    Anal Biochem 370:223-7. 2007
    ..This suggests that the Ellman method cannot be used uncritically to evaluate oxime reaction with choline esters, in particular when oximolysis is faster than the Ellman reaction itself at a given pH...
  26. ncbi request reprint para- and ortho-Pyridinium aldoximes in reaction with acetylthiocholine
    Goran Sinko
    Institute for Medical Research and Occupational Health, POB 291, HR 10 001 Zagreb, Croatia
    FEBS Lett 580:3167-72. 2006
    ..Thermodynamic parameters, DeltaG#, DeltaH# and DeltaS#, were also determined for oximolysis reaction...
  27. ncbi request reprint Acetylcholinesterase mutants: oxime-assisted catalytic scavengers of organophosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Chem Biol Interact 157:388-90. 2005
  28. pmc Acetylcholinesterase active centre and gorge conformations analysed by combinatorial mutations and enantiomeric phosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Biochem J 373:33-40. 2003
    ..Rather, the individual aromatic residues may mutually interact to confer a distinctive stereospecificity pattern towards organophosphates...
  29. ncbi request reprint Preparative HPLC separation of bambuterol enantiomers and stereoselective inhibition of human cholinesterases
    Ivana Gazić
    Ruder Boskovic Institute, Bijenicka cesta 54, 10002, Zagreb, Croatia
    Anal Bioanal Chem 385:1513-9. 2006
    ..4 to 0.11 min(-1)microM(-1). The inhibition rates for heterozygotes were between the respective constants for the corresponding homozygotes...
  30. ncbi request reprint Mutation of acetylcholinesterase to enhance oxime-assisted catalytic turnover of methylphosphonates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, CA 92093 0636, USA
    Toxicology 233:79-84. 2007
    ..Our results confirm that a mixture of a mutant enzyme and an oxime might serve as an in vivo catalytic scavenger of organophosphates...
  31. pmc Acetylcholinesterase: converting a vulnerable target to a template for antidotes and detection of inhibitor exposure
    Palmer Taylor
    Department of Pharmacology, Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0650, USA
    Toxicology 233:70-8. 2007
    ..Since external reagents do not have to be added to detect the fluorescence change, the modified enzyme would serve as a remote sensor...
  32. ncbi request reprint A mutation linked with autism reveals a common mechanism of endoplasmic reticulum retention for the alpha,beta-hydrolase fold protein family
    Antonella De Jaco
    Department of Pharmacology, University of California San Diego, La Jolla, California 92093 0636, USA
    J Biol Chem 281:9667-76. 2006
    ..The mutation may alter the capacity of these proteins to dissociate from their chaperone prior to oligomerization and processing for export...
  33. ncbi request reprint Application of recombinant DNA methods for production of cholinesterases as organophosphate antidotes and detectors
    Palmer Taylor
    Skaggs School of Pharmacy and Pharmaceutical Sciences, University of California, San Diego, La Jolla, CA 92093 0657, USA
    Arh Hig Rada Toksikol 58:339-45. 2007
    ....
  34. ncbi request reprint Mutant cholinesterases possessing enhanced capacity for reactivation of their phosphonylated conjugates
    Zrinka Kovarik
    Department of Pharmacology, University of California at San Diego, La Jolla, California 92093 0636, USA
    Biochemistry 43:3222-9. 2004
    ..Rates of reactivation reach values sufficient for consideration of mixtures of a mutant enzyme and an oxime as a scavenging strategy in protection and treatment of organophosphate exposure...