@conference{
author = "Nedeljković, Nikola and Dobričić, Vladimir and Mijajlović, Marina and Radić, Gordana and Nikolić, Miloš and Stanković, Ana and Vujić, Zorica",
year = "2021",
abstract = "Masking the carboxyl group of naproxen with other functional groups may be a
promising strategy to decrease its gastrointestinal toxicity. Thiourea moiety has been described
as an important pharmacophore in a variety of pharmacologically active compounds, including
anti-inflammatory, antiviral, anticancer, hypoglycemic and antimicrobial agents. Our research
group has previously designed twenty novel thiourea derivatives of naproxen, containing amino
acids (glycine, L-alanine, β-alanine, L-valine and L-phenylalanine - compounds 1,2,3,4 and 5,
respectively), their methyl (6-10) and ethyl esters (11-15), as well as aromatic amines (16-20).
Pharmacokinetic properties and druglikeness of these compounds were predicted using
SwissADME web tool (http://www.swissadme.ch/). Predicted pharmacokinetic properties
include potential for gastrointestinal absorption, blood-brain barrier permeability, skin
permeability, transport mediated by P-glycoproteins and enzyme inhibitory potential.
Druglikeness was evaluated using Lipinski’s, Ghose’s, Veber’s, Egan’s and Muegge’s rules, as
well as on the basis of bioavailability score. All tested compounds had high-predicted
gastrointestinal absorption and low blood-brain barrier permeability. Also, derivatives 2, 4, 7,
9, 10, 12, 14, 15 and 18 were predicted to be substrates for P-glycoprotein. Derivatives with
aromatic amines (16-20) showed inhibitory potential against all tested CYP isoforms.
Derivative 19 had the highest, while derivative 13 demonstrated the lowest predicted skin
permeability. Finally, derivatives 1-12, except 5 and 10, have druglike structures, since they
obey to all imposed rules.",
publisher = "Institute for Information Technologies, University of Kragujevac, Serbia",
journal = "1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings",
title = "In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen",
pages = "371-374",
doi = "10.46793/ICCBI21.371N"
}