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Pregled bibliografske jedinice broj: 1011823

Time-dependent cytotoxicity of pyridinium antidotes

Zandona, Antonio; Madunić Josip; Katalinić, Maja
Time-dependent cytotoxicity of pyridinium antidotes // Final Programme of the 44th FEBS Congress and Book of Abstract at the 19th YSF FEBS 2019, Krakow, Poland
Krakow, Poland, 2019. str. 46-46 (poster, međunarodna recenzija, sažetak, znanstveni)

Time-dependent cytotoxicity of pyridinium antidotes

Zandona, Antonio ; Madunić Josip ; Katalinić, Maja

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Final Programme of the 44th FEBS Congress and Book of Abstract at the 19th YSF FEBS 2019, Krakow, Poland / - , 2019, 46-46

The 44th FEBS Congress and the 19th FEBS Young Scientists' Forum 2019

Mjesto i datum
Krakow, Poland, 03-11.07.2019

Vrsta sudjelovanja

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Time-dependent, cytotoxicity, oximes, pyridinium, antidotes

The better selection of a lead candidate for preclinical drug development has come into strong demand in recent years. In that sense, early, rapid and robust results, that unambiguously rank compounds for their desirable and undesirable effects, put cell- based in vitro toxicology in major focus. In the preclinical selection of the most efficient antidotes for organophosphorus pesticide and nerve warfare agents poisoning, we evaluated the time-dependent cytotoxicity of the leading oxime compounds. We evaluated a structurally dependent series of oximes bearing up to two chlorine atoms that showed a promising antidote potential in the previous studies. The cytotoxic effect was evaluated on several cell lines in a wide oxime concentration range and at least three time points. The results were compared to the oxime HI-6, which is used today as an antidote in medical practice. As results indicate, time-dependent toxicity of tested oximes was strongly related to their structure and the ones having both a but-2(E)-en-1, 4-diyl linker and chlorine atoms were the most toxic to all cells tested. The IC50 determined by the MTS assay was in the μM range. This effect was also confirmed by additionally testing the ATP status of the cells. Though the mechanism behind this toxicity needs to be confirmed, such a result indicates that these oximes have limitations if considered for further antidote development. Acknowledgment: This work was supported in part by the Croatian Science Foundation under the project UIP-2017-05-7260.

Izvorni jezik

Znanstvena područja
Kemija, Biologija


Projekt / tema

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