TY  - JOUR
AU  - Dobričić, Vladimir
AU  - Marodi, Marko
AU  - Marković, Bojan
AU  - Tomašič, Tihomir
AU  - Durcik, Martina
AU  - Zidar, Nace
AU  - Mašič, Peterlin L.
AU  - Ilaš, Janez
AU  - Kikelj, Danijel
AU  - Čudina, Olivera
PY  - 2024
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5644
AB  - DNA gyrase and topoisomerase IV play significant role in maintaining the correct structure of DNA during replication and they have been identified as validated targets in antibacterial drug discovery. Inadequate pharmacokinetic properties are responsible for many failures during drug discovery and their estimation in the early phase of this process maximizes the chance of getting useful drug candidates. Passive gastrointestinal absorption of a selected group of thirteen dual DNA gyrase and topoisomerase IV inhibitors was estimated using two in vitro tests – parallel artificial membrane permeability assay (PAMPA) and biopartitioning micellar chromatography (BMC). Due to good correlation between obtained results, passive gastrointestinal absorption of remaining ten compounds was estimated using only BMC. With this experimental setup, it was possible to identify compounds with high values of retention factors (k) and highest expected passive gastrointestinal absorption, and compounds with low values of k for which low passive gastrointestinal absorption is predicted. Quantitative structure-retention relationship (QSRR) modelling was performed by creating multiple linear regression (MLR), partial least squares (PLS) and support vector machines (SVM) models. Descriptors with the highest influence on retention factor were identified and their interpretation can be used for the design of new compounds with improved passive gastrointestinal absorption.
PB  - Estimation of passive gastrointestinal absorption of new dual DNA gyrase and topoisomerase IV inhibitors using PAMPA and biopartitioning micellar chromatography and quantitative structure-retention relationship analysis
T2  - Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
T1  - Estimation of passive gastrointestinal absorption of new dual DNA gyrase and topoisomerase IV inhibitors using PAMPA and biopartitioning micellar chromatography and quantitative structure-retention relationship analysis
VL  - 1240
DO  - 10.1016/j.jchromb.2024.124158
ER  - 

@article{
author = "Dobričić, Vladimir and Marodi, Marko and Marković, Bojan and Tomašič, Tihomir and Durcik, Martina and Zidar, Nace and Mašič, Peterlin L. and Ilaš, Janez and Kikelj, Danijel and Čudina, Olivera",
year = "2024",
abstract = "DNA gyrase and topoisomerase IV play significant role in maintaining the correct structure of DNA during replication and they have been identified as validated targets in antibacterial drug discovery. Inadequate pharmacokinetic properties are responsible for many failures during drug discovery and their estimation in the early phase of this process maximizes the chance of getting useful drug candidates. Passive gastrointestinal absorption of a selected group of thirteen dual DNA gyrase and topoisomerase IV inhibitors was estimated using two in vitro tests – parallel artificial membrane permeability assay (PAMPA) and biopartitioning micellar chromatography (BMC). Due to good correlation between obtained results, passive gastrointestinal absorption of remaining ten compounds was estimated using only BMC. With this experimental setup, it was possible to identify compounds with high values of retention factors (k) and highest expected passive gastrointestinal absorption, and compounds with low values of k for which low passive gastrointestinal absorption is predicted. Quantitative structure-retention relationship (QSRR) modelling was performed by creating multiple linear regression (MLR), partial least squares (PLS) and support vector machines (SVM) models. Descriptors with the highest influence on retention factor were identified and their interpretation can be used for the design of new compounds with improved passive gastrointestinal absorption.",
publisher = "Estimation of passive gastrointestinal absorption of new dual DNA gyrase and topoisomerase IV inhibitors using PAMPA and biopartitioning micellar chromatography and quantitative structure-retention relationship analysis",
journal = "Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences",
title = "Estimation of passive gastrointestinal absorption of new dual DNA gyrase and topoisomerase IV inhibitors using PAMPA and biopartitioning micellar chromatography and quantitative structure-retention relationship analysis",
volume = "1240",
doi = "10.1016/j.jchromb.2024.124158"
}

Dobričić, V., Marodi, M., Marković, B., Tomašič, T., Durcik, M., Zidar, N., Mašič, P. L., Ilaš, J., Kikelj, D.,& Čudina, O.. (2024). Estimation of passive gastrointestinal absorption of new dual DNA gyrase and topoisomerase IV inhibitors using PAMPA and biopartitioning micellar chromatography and quantitative structure-retention relationship analysis. in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences
Estimation of passive gastrointestinal absorption of new dual DNA gyrase and topoisomerase IV inhibitors using PAMPA and biopartitioning micellar chromatography and quantitative structure-retention relationship analysis., 1240.
https://doi.org/10.1016/j.jchromb.2024.124158

Dobričić V, Marodi M, Marković B, Tomašič T, Durcik M, Zidar N, Mašič PL, Ilaš J, Kikelj D, Čudina O. Estimation of passive gastrointestinal absorption of new dual DNA gyrase and topoisomerase IV inhibitors using PAMPA and biopartitioning micellar chromatography and quantitative structure-retention relationship analysis. in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences. 2024;1240.
doi:10.1016/j.jchromb.2024.124158 .

Dobričić, Vladimir, Marodi, Marko, Marković, Bojan, Tomašič, Tihomir, Durcik, Martina, Zidar, Nace, Mašič, Peterlin L., Ilaš, Janez, Kikelj, Danijel, Čudina, Olivera, "Estimation of passive gastrointestinal absorption of new dual DNA gyrase and topoisomerase IV inhibitors using PAMPA and biopartitioning micellar chromatography and quantitative structure-retention relationship analysis" in Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 1240 (2024),
https://doi.org/10.1016/j.jchromb.2024.124158 . .

TY  - CONF
AU  - Dobričić, Vladimir
AU  - Marodi, Marko
AU  - Marković, Bojan
AU  - Tomašič, Tihomir
AU  - Zidar, Nace
AU  - Peterlin Mašič, Lucija
AU  - Ilaš, Janez
AU  - Kikelj, Danijel
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/5460
AB  - In this study, estimation of gastrointestinal absorption of thirteen selected dual DNA gyrase and topoisomerase IV
inhibitors was carried out using PAMPA test. Diffusion through artificial membrane, consisting of egg lecithin solution
in dodecane (first PAMPA model) and a mixture of hexadecane and hexane (second PAMPA model), was monitored
[1,2]. The starting solutions (pH 5.5) and the acceptor medium (pH 7.4) were prepared to contain 2% dimethyl
sulfoxide. Concentrations of tested compounds in starting solutions, donor and acceptor medium after incubation
were measured using LC-MS/MS method. Permeability coefficients were calculated and good correlation was
observed between results obtained using these two PAMPA models. Subsequently, the hexadecane/hexane model
was selected for the evaluation of gastrointestinal absorption of the remaining ten compounds.
Derivatives with the highest permeability in hexadecane/hexane model were TZS-34 and TCF-3a (logPe: -5.37 and
-4.93, respectively) whereas TLK-13 and NZ-97 had the lowest permeability (logPe: -9.91 and -9.85, respectively).
Therefore, the highest gastrointestinal absorption can be expected from TZS-34 and TCF-3a, and lowest from TLK-13
and NZ-97 (Figure 1). High membrane retention observed for compounds TEL-28 (72%) and TAZ-2b (30 %) might be a
reason for lower permeability than expected based on their lipophilicity.
PB  - MuTaLig COST ACTION CA15135
C3  - Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts
T1  - Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique
SP  - 41
EP  - 41
UR  - https://hdl.handle.net/21.15107/rcub_farfar_5460
ER  - 

@conference{
author = "Dobričić, Vladimir and Marodi, Marko and Marković, Bojan and Tomašič, Tihomir and Zidar, Nace and Peterlin Mašič, Lucija and Ilaš, Janez and Kikelj, Danijel",
year = "2020",
abstract = "In this study, estimation of gastrointestinal absorption of thirteen selected dual DNA gyrase and topoisomerase IV
inhibitors was carried out using PAMPA test. Diffusion through artificial membrane, consisting of egg lecithin solution
in dodecane (first PAMPA model) and a mixture of hexadecane and hexane (second PAMPA model), was monitored
[1,2]. The starting solutions (pH 5.5) and the acceptor medium (pH 7.4) were prepared to contain 2% dimethyl
sulfoxide. Concentrations of tested compounds in starting solutions, donor and acceptor medium after incubation
were measured using LC-MS/MS method. Permeability coefficients were calculated and good correlation was
observed between results obtained using these two PAMPA models. Subsequently, the hexadecane/hexane model
was selected for the evaluation of gastrointestinal absorption of the remaining ten compounds.
Derivatives with the highest permeability in hexadecane/hexane model were TZS-34 and TCF-3a (logPe: -5.37 and
-4.93, respectively) whereas TLK-13 and NZ-97 had the lowest permeability (logPe: -9.91 and -9.85, respectively).
Therefore, the highest gastrointestinal absorption can be expected from TZS-34 and TCF-3a, and lowest from TLK-13
and NZ-97 (Figure 1). High membrane retention observed for compounds TEL-28 (72%) and TAZ-2b (30 %) might be a
reason for lower permeability than expected based on their lipophilicity.",
publisher = "MuTaLig COST ACTION CA15135",
journal = "Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts",
title = "Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique",
pages = "41-41",
url = "https://hdl.handle.net/21.15107/rcub_farfar_5460"
}

Dobričić, V., Marodi, M., Marković, B., Tomašič, T., Zidar, N., Peterlin Mašič, L., Ilaš, J.,& Kikelj, D.. (2020). Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique. in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts
MuTaLig COST ACTION CA15135., 41-41.
https://hdl.handle.net/21.15107/rcub_farfar_5460

Dobričić V, Marodi M, Marković B, Tomašič T, Zidar N, Peterlin Mašič L, Ilaš J, Kikelj D. Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique. in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts. 2020;:41-41.
https://hdl.handle.net/21.15107/rcub_farfar_5460 .

Dobričić, Vladimir, Marodi, Marko, Marković, Bojan, Tomašič, Tihomir, Zidar, Nace, Peterlin Mašič, Lucija, Ilaš, Janez, Kikelj, Danijel, "Estimation of gastrointestinal absorption of a series of dual DNA Gyrase and Topoisomerase IV inhibitors using Pampa technique" in Fourth WG Meeting CA15135, Cost Action CA15135, 5 - 7. March, 2020. Bornova, Izmir, Book of the Abstracts (2020):41-41,
https://hdl.handle.net/21.15107/rcub_farfar_5460 .