Naslov
Pharmacophore models to predict oxime antidote interactions with specific cell targets

Autori
Maraković, Nikola ; Katalinić, Maja

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

Izvornik
Book of Abstract of the Congress of the Croatian Society of Biochemistry and Molecular Biology "Crossroads in Life Sciences", HDBMB2019 / Katalnić, Maja ; Dulić, Morana ; Stuparević, Igor - , 2019, 100-100

ISBN
978-953-95551-7-5

Skup
Congress of the Croatian Society of Biochemistry and Molecular Biology "Crossroads in Life Sciences" (HDBMB2019)

Mjesto i datum
Lovran, Hrvatska, 25.09.2019. - 28.09.2019

Vrsta sudjelovanja
Poster

Vrsta recenzije
Domaća recenzija

Ključne riječi
oximes ; computational chemistry, modelling, targets

Sažetak
To identify specific cell targets that interfere with the antidotal activity of different series of oxime reactivators of organophosphorus-inhibited acetylcholinesterase including quinuclidinium oximes, imidazolium oximes, bispiridinium oximes, and 3-hydroxy-2- pirisdiniumaldoximes, we generated a pharmacophore model for each series. More precisely, using the 3D QSAR Pharmacophore Generation protocol as implemented in the Biovia Discovery Studio Client software package, we modeled a pharmacophore model from a set of molecules from a given series together with known activity values. For activity values, we used the IC50 values of the tested compound against all of the following cell lines: SH-SY5Y, HepG2, HK-2, and Myoblasts. A test set from each series was chosen to cover activity values that spanned at least 3 orders of magnitude. With the generated pharmacophore model, we ran the Search 3D Database protocol which uses Catalyst to identify ligands that map to a generated pharmacophore from the database carrying information about associated cell targets and mechanisms of action responsible for the observed biological phenotype. The highest scored ligands that best fit a pharmacophore were closely inspected for their cell targets. The provided information will subsequently be used to narrow down the choice of possible cell targets of the tested oxime reactivators and experimental methods used to ascertain the assumed interaction. Acknowledgment: This work was supported in part by the Croatian Science Foundation under the project UIP-2017-05-7260.

Izvorni jezik
Engleski

Znanstvena područja
Kemija, Biologija

POVEZANOST RADA