Naslov
Structure – cytotoxicity relationship of cholinesterase-based ligands

Autori
Zandona, Antonio

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

Izvornik
Arhiv za higijenu rada i toksikologiju / - , 2023, A11-A11

Skup
Cell-Based Research in Toxicology and Drug Design

Mjesto i datum
Zagreb, Hrvatska, 26.01.2023

Vrsta sudjelovanja
Pozvano predavanje

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
cytotoxicity ; apoptotis ; caspase ; oximes

Sažetak
Oximes and new classes of compounds are being investigated as antidotes in the therapy of poisoning with organophosphorus compounds or as drugs for neurodegenerative diseases. In current research, the leading candidates, chosen solely on the basis of in vitro kinetic studies, are tested immediately on animal models in vivo where they often cause side effects or toxicity, which is why they are excluded from further testing. In this way, unnecessary tests on animals are carried out with a large consumption of resources, and valuable data on the effects at the cellular level are lost. A new approach to antidote/drug evaluation, based on cellular assays, would screen compounds with desirable characteristics for further development of new antidote/drug. In this way, the toxic effect can be examined at the cellular level and linked to specific structural elements of the compound, with the aim of defining guidelines for improving the structure of oxime in the early phase of research into their effectiveness as an antidote without conducting in vivo studies. By defining the relationship between the structure and cytotoxicity of the tested compounds and by determining the mechanism of action at the cellular level, new possible pharmacological targets can be determined, as well as the possibility of researching their therapeutic potential. This research was supported by the Croatian Science Foundation UIP-2017-05-7260 and Slovenian Research Agency (J3-3065 to S.P. and J3-2523, P3-0043 and J7-3153 to S.P. and K.M), Croatian-Slovenian Bilateral grant 2020-2021 (BI- HR/20-21-041). Part of this work was supported through the EMBO short term fellowship STF-8731 to A. Zandona in M. Castanho lab (Lisabon, Portugal) and Foundation of the Croatian Academy of Sciences and Arts (10- 102/414-254-2018 and 10-102/384-263-2020)

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA