In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen
Аутори
Nedeljković, NikolaDobričić, Vladimir
Mijajlović, Marina
Radić, Gordana
Nikolić, Miloš
Stanković, Ana
Vujić, Zorica
Конференцијски прилог (Објављена верзија)
Метаподаци
Приказ свих података о документуАпстракт
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.
D...ruglikeness 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.
Кључне речи:
naproxen / thiourea derivatives / pharmacokinetic properties / druglikeness / SwissADMEИзвор:
1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings, 2021, 371-374Издавач:
- Institute for Information Technologies, University of Kragujevac, Serbia
Институција/група
PharmacyTY - CONF AU - Nedeljković, Nikola AU - Dobričić, Vladimir AU - Mijajlović, Marina AU - Radić, Gordana AU - Nikolić, Miloš AU - Stanković, Ana AU - Vujić, Zorica PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5474 AB - 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. PB - Institute for Information Technologies, University of Kragujevac, Serbia C3 - 1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings T1 - In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen SP - 371 EP - 374 DO - 10.46793/ICCBI21.371N ER -
@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" }
Nedeljković, N., Dobričić, V., Mijajlović, M., Radić, G., Nikolić, M., Stanković, A.,& Vujić, Z.. (2021). In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen. in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings Institute for Information Technologies, University of Kragujevac, Serbia., 371-374. https://doi.org/10.46793/ICCBI21.371N
Nedeljković N, Dobričić V, Mijajlović M, Radić G, Nikolić M, Stanković A, Vujić Z. In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen. in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings. 2021;:371-374. doi:10.46793/ICCBI21.371N .
Nedeljković, Nikola, Dobričić, Vladimir, Mijajlović, Marina, Radić, Gordana, Nikolić, Miloš, Stanković, Ana, Vujić, Zorica, "In silico prediction of pharmacokinetic properties and druglikeness of novel thiourea derivatives of naproxen" in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021, October 26 - 27th, 2021, Kragujevac, Serbia, Book of Proceedings (2021):371-374, https://doi.org/10.46793/ICCBI21.371N . .