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  - JOUR
AU  - Hendrickx, Louise Antonia
AU  - Dobričić, Vladimir
AU  - Toplak, Žan
AU  - Peigneur, Steve
AU  - Peterlin Mašič, Lucija
AU  - Tomašič, Tihomir
AU  - Tytgat, Jan
PY  - 2020
UR  - https://farfar.pharmacy.bg.ac.rs/handle/123456789/3568
AB  - The voltage-gated potassium channel Kv1.3 is involved in multiple autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, diabetes mellitus type 1 and psoriasis. In many auto-immune diseases better treatment options are desired as existing therapies are often ineffective or become less effective over time, for which Kv1.3 inhibitors arise as promising candidates. In this study, five compounds were selected based on a 3D similarity searching methodology and subsequently screened ex vivo on the Kv1.3 channel. The screening resulted in two compounds inhibiting the Kv1.3 channel, of which TVS-12 was the most potent compound, while TVS-06 -although less potent- showed an excellent selectivity for Kv1.3. For both compounds the mechanism of action was investigated by an electrophysiological characterization on the Kv1.3 channel and three Kv1.3 mutants, designed to resemble the pore region of Kv1.2 channels. Structurally, the presence of a benzene ring and/or an oxane ring seems to cause a better interaction with the Kv1.3 channel, resulting in a 20-fold higher potency for TVS-12.
PB  - Elsevier
T2  - Bioorganic Chemistry
T1  - Design and characterization of a novel structural class of Kv1.3 inhibitors
VL  - 98
DO  - 10.1016/j.bioorg.2020.103746
ER  - 

@article{
author = "Hendrickx, Louise Antonia and Dobričić, Vladimir and Toplak, Žan and Peigneur, Steve and Peterlin Mašič, Lucija and Tomašič, Tihomir and Tytgat, Jan",
year = "2020",
abstract = "The voltage-gated potassium channel Kv1.3 is involved in multiple autoimmune diseases, such as multiple sclerosis, rheumatoid arthritis, diabetes mellitus type 1 and psoriasis. In many auto-immune diseases better treatment options are desired as existing therapies are often ineffective or become less effective over time, for which Kv1.3 inhibitors arise as promising candidates. In this study, five compounds were selected based on a 3D similarity searching methodology and subsequently screened ex vivo on the Kv1.3 channel. The screening resulted in two compounds inhibiting the Kv1.3 channel, of which TVS-12 was the most potent compound, while TVS-06 -although less potent- showed an excellent selectivity for Kv1.3. For both compounds the mechanism of action was investigated by an electrophysiological characterization on the Kv1.3 channel and three Kv1.3 mutants, designed to resemble the pore region of Kv1.2 channels. Structurally, the presence of a benzene ring and/or an oxane ring seems to cause a better interaction with the Kv1.3 channel, resulting in a 20-fold higher potency for TVS-12.",
publisher = "Elsevier",
journal = "Bioorganic Chemistry",
title = "Design and characterization of a novel structural class of Kv1.3 inhibitors",
volume = "98",
doi = "10.1016/j.bioorg.2020.103746"
}

Hendrickx, L. A., Dobričić, V., Toplak, Ž., Peigneur, S., Peterlin Mašič, L., Tomašič, T.,& Tytgat, J.. (2020). Design and characterization of a novel structural class of Kv1.3 inhibitors. in Bioorganic Chemistry
Elsevier., 98.
https://doi.org/10.1016/j.bioorg.2020.103746

Hendrickx LA, Dobričić V, Toplak Ž, Peigneur S, Peterlin Mašič L, Tomašič T, Tytgat J. Design and characterization of a novel structural class of Kv1.3 inhibitors. in Bioorganic Chemistry. 2020;98.
doi:10.1016/j.bioorg.2020.103746 .

Hendrickx, Louise Antonia, Dobričić, Vladimir, Toplak, Žan, Peigneur, Steve, Peterlin Mašič, Lucija, Tomašič, Tihomir, Tytgat, Jan, "Design and characterization of a novel structural class of Kv1.3 inhibitors" in Bioorganic Chemistry, 98 (2020),
https://doi.org/10.1016/j.bioorg.2020.103746 . .