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Pregled bibliografske jedinice broj: 1134026

Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes


Zandona, Antonio; Maraković, Nikola; Mišetić, Petra; Madunić, Josip; Miš, Katarina; Padovan, Jasna; Pirkmajer, Sergej; Katalinić, Maja
Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes // Archives of toxicology, 95 (2021), 2737-2754 doi:10.1007/s00204-021-03098-w (međunarodna recenzija, članak, znanstveni)


CROSBI ID: 1134026 Za ispravke kontaktirajte CROSBI podršku putem web obrasca

Naslov
Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes

Autori
Zandona, Antonio ; Maraković, Nikola ; Mišetić, Petra ; Madunić, Josip ; Miš, Katarina ; Padovan, Jasna ; Pirkmajer, Sergej ; Katalinić, Maja

Izvornik
Archives of toxicology (0340-5761) 95 (2021); 2737-2754

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

Ključne riječi
Oximes ; Cytotoxicity ; Pharmacophore ; Caspase ; Permeability ; Apoptosis
(oximes ; cytotoxicity ; pharmacophore ; caspase ; permeability ; apoptosis)

Sažetak
Oximes, investigated as antidotes against organophosphates (OP) poisoning, are known to display toxic effects on a cellular level, which could be explained beyond action on acetylcholinesterase as their main target. To investigate this further, we performed an in vitro cell-based evaluation of effects of two structurally diverse oxime groups at concentrations of up to 800 μM, on several cell models: skeletal muscle, kidney, liver, and neural cells. As indicated by our results, compounds with an imidazolium core induced necrosis, unregulated cell death characterized by a cell burst, increased formation of reactive oxygen species, and activation of antioxidant scavenging. On the other hand, oximes with a pyridinium core activated apoptosis through specific caspases 3, 8, and/or 9. Interestingly, some of the compounds exhibited a synergistic effect. Moreover, we generated a pharmacophore model for each oxime series and identified ligands from public databases that map to generated pharmacophores. Several interesting hits were obtained including chemotherapeutics and specific inhibitors. We were able to define the possible structural features of tested oximes triggering toxic effects: chlorine atoms in combination with but-2(E)-en-1, 4-diyl linker and adding a second benzene ring with substituents such as chlorine and/or methyl on the imidazolium core. Such oximes could not be used in further OP antidote development research, but could be introduced in other research studies on new specific targets. This could undoubtedly result in an overall improved wider use of unexplored oxime database created so far in OP antidotes field of research in a completely new perspective.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija



POVEZANOST RADA


Projekti:
UIP-2017-05-7260 - MOLEKULARNI MEHANIZMI TOKSIČNOSTI PROTUOTROVA I POTENCIJALNIH LIJEKOVA (CellToxTargets) (Katalinić, Maja, HRZZ - 2017-05) ( POIROT)

Ustanove:
Institut za medicinska istraživanja i medicinu rada, Zagreb,
Fidelta d.o.o.

Poveznice na cjeloviti tekst rada:

doi

Citiraj ovu publikaciju:

Zandona, Antonio; Maraković, Nikola; Mišetić, Petra; Madunić, Josip; Miš, Katarina; Padovan, Jasna; Pirkmajer, Sergej; Katalinić, Maja
Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes // Archives of toxicology, 95 (2021), 2737-2754 doi:10.1007/s00204-021-03098-w (međunarodna recenzija, članak, znanstveni)
Zandona, A., Maraković, N., Mišetić, P., Madunić, J., Miš, K., Padovan, J., Pirkmajer, S. & Katalinić, M. (2021) Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes. Archives of toxicology, 95, 2737-2754 doi:10.1007/s00204-021-03098-w.
@article{article, author = {Zandona, Antonio and Marakovi\'{c}, Nikola and Mi\v{s}eti\'{c}, Petra and Maduni\'{c}, Josip and Mi\v{s}, Katarina and Padovan, Jasna and Pirkmajer, Sergej and Katalini\'{c}, Maja}, year = {2021}, pages = {2737-2754}, DOI = {10.1007/s00204-021-03098-w}, keywords = {Oximes, Cytotoxicity, Pharmacophore, Caspase, Permeability, Apoptosis}, journal = {Archives of toxicology}, doi = {10.1007/s00204-021-03098-w}, volume = {95}, issn = {0340-5761}, title = {Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes}, keyword = {Oximes, Cytotoxicity, Pharmacophore, Caspase, Permeability, Apoptosis} }
@article{article, author = {Zandona, Antonio and Marakovi\'{c}, Nikola and Mi\v{s}eti\'{c}, Petra and Maduni\'{c}, Josip and Mi\v{s}, Katarina and Padovan, Jasna and Pirkmajer, Sergej and Katalini\'{c}, Maja}, year = {2021}, pages = {2737-2754}, DOI = {10.1007/s00204-021-03098-w}, keywords = {oximes, cytotoxicity, pharmacophore, caspase, permeability, apoptosis}, journal = {Archives of toxicology}, doi = {10.1007/s00204-021-03098-w}, volume = {95}, issn = {0340-5761}, title = {Activation of (un)regulated cell death as a new perspective for bispyridinium and imidazolium oximes}, keyword = {oximes, cytotoxicity, pharmacophore, caspase, permeability, apoptosis} }

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


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