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
Authorized Users Only
2024
Authors
Dobričić, VladimirMarodi, Marko
Marković, Bojan
Tomašič, Tihomir
Durcik, Martina
Zidar, Nace
Mašič, Peterlin L.
Ilaš, Janez
Kikelj, Danijel
Čudina, Olivera
Article (Published version)
Metadata
Show full item recordAbstract
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.
Keywords:
PAMPA / Biopartitioning micellar chromatography / Drug design / Passive gastrointestinal absorption / Quantitative structure-retention relationship analysisSource:
Journal of Chromatography B: Analytical Technologies in the Biomedical and Life Sciences, 2024, 1240Publisher:
- 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
Funding / projects:
- Ministry of Science, Technological Development and Innovation of the Republic of Serbia, institutional funding - 200161 (University of Belgrade, Faculty of Pharmacy) (RS-MESTD-inst-2020-200161)
- Slovenian Research Agency (Grant No. P1-0208 and Grant No. J1-3031)
- The project of bilateral cooperation between Republic of Slovenia and Republic of Serbia (BI-RS/18-19-034)
DOI: 10.1016/j.jchromb.2024.124158
ISSN: 1570-0232
PubMed: 38776787
Scopus: 2-s2.0-85193581202
Collections
Institution/Community
PharmacyTY - 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 . .