The molecular basis of drug-plasma protein interaction for CNS active compounds
Апстракт
The human serum albumin (HSA) is well known for its extraordinary binding capacity
for both endogenous and exogenous compounds, including a wide range of drugs. The goal of
our investigation was to evaluate the distribution process for 15 CNS active compounds. The
drug-plasma protein interaction was evaluated under simulative physiological conditions on the
HSA-based stationary phase by using the mixture of Sørensen phosphate buffer (pH 7.40) and
acetonitrile modifier as a mobile phase (84:16 v/v). The retention parameters (k) were used to
approximate the % of protein-binding by calculating the P(%) values. The results obtained
through this study demonstrated that the constitutional properties (e.g. number of total bonds,
atoms, carbon atoms) and lipophilicity have a strong positive impact on the HSA-binding
affinity. The coefficient of diffusion has a negative impact, while the atoms and sites available
for the CYP450 oxidation showed the most significant correlation (r = 0....92). This study
provides a basis for further in vitro chromatographical investigations of drug-HSA interaction
for CNS active compounds. The correlation between obtained retention data and the availability
to enzymes oxidation indicates the application of the tested system in the assessment of the
metabolic degradation profile of CNS related drugs.
Кључне речи:
human serum albumin / binding affinity / CNS compounds / molecular characterizationИзвор:
1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS), 2021, 375-378Издавач:
- Institute for Information Technologies, University of Kragujevac, Serbia
Финансирање / пројекти:
- Министарство науке, технолошког развоја и иновација Републике Србије, институционално финансирање - 200161 (Универзитет у Београду, Фармацеутски факултет) (RS-MESTD-inst-2020-200161)
Напомена:
- 1st International Conference on Chemo and BioInformatics, Kragujevac, October 26-27, 2021 Serbia
Институција/група
PharmacyTY - CONF AU - Obradović, Darija AU - Radan, Milica AU - Popović-Nikolić, Marija AU - Oljačić, Slavica AU - Nikolić, Katarina PY - 2021 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/4686 AB - The human serum albumin (HSA) is well known for its extraordinary binding capacity for both endogenous and exogenous compounds, including a wide range of drugs. The goal of our investigation was to evaluate the distribution process for 15 CNS active compounds. The drug-plasma protein interaction was evaluated under simulative physiological conditions on the HSA-based stationary phase by using the mixture of Sørensen phosphate buffer (pH 7.40) and acetonitrile modifier as a mobile phase (84:16 v/v). The retention parameters (k) were used to approximate the % of protein-binding by calculating the P(%) values. The results obtained through this study demonstrated that the constitutional properties (e.g. number of total bonds, atoms, carbon atoms) and lipophilicity have a strong positive impact on the HSA-binding affinity. The coefficient of diffusion has a negative impact, while the atoms and sites available for the CYP450 oxidation showed the most significant correlation (r = 0.92). This study provides a basis for further in vitro chromatographical investigations of drug-HSA interaction for CNS active compounds. The correlation between obtained retention data and the availability to enzymes oxidation indicates the application of the tested system in the assessment of the metabolic degradation profile of CNS related drugs. PB - Institute for Information Technologies, University of Kragujevac, Serbia C3 - 1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS) T1 - The molecular basis of drug-plasma protein interaction for CNS active compounds SP - 375 EP - 378 DO - 10.46793/ICCBI21.375O ER -
@conference{ author = "Obradović, Darija and Radan, Milica and Popović-Nikolić, Marija and Oljačić, Slavica and Nikolić, Katarina", year = "2021", abstract = "The human serum albumin (HSA) is well known for its extraordinary binding capacity for both endogenous and exogenous compounds, including a wide range of drugs. The goal of our investigation was to evaluate the distribution process for 15 CNS active compounds. The drug-plasma protein interaction was evaluated under simulative physiological conditions on the HSA-based stationary phase by using the mixture of Sørensen phosphate buffer (pH 7.40) and acetonitrile modifier as a mobile phase (84:16 v/v). The retention parameters (k) were used to approximate the % of protein-binding by calculating the P(%) values. The results obtained through this study demonstrated that the constitutional properties (e.g. number of total bonds, atoms, carbon atoms) and lipophilicity have a strong positive impact on the HSA-binding affinity. The coefficient of diffusion has a negative impact, while the atoms and sites available for the CYP450 oxidation showed the most significant correlation (r = 0.92). This study provides a basis for further in vitro chromatographical investigations of drug-HSA interaction for CNS active compounds. The correlation between obtained retention data and the availability to enzymes oxidation indicates the application of the tested system in the assessment of the metabolic degradation profile of CNS related drugs.", publisher = "Institute for Information Technologies, University of Kragujevac, Serbia", journal = "1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS)", title = "The molecular basis of drug-plasma protein interaction for CNS active compounds", pages = "375-378", doi = "10.46793/ICCBI21.375O" }
Obradović, D., Radan, M., Popović-Nikolić, M., Oljačić, S.,& Nikolić, K.. (2021). The molecular basis of drug-plasma protein interaction for CNS active compounds. in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS) Institute for Information Technologies, University of Kragujevac, Serbia., 375-378. https://doi.org/10.46793/ICCBI21.375O
Obradović D, Radan M, Popović-Nikolić M, Oljačić S, Nikolić K. The molecular basis of drug-plasma protein interaction for CNS active compounds. in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS). 2021;:375-378. doi:10.46793/ICCBI21.375O .
Obradović, Darija, Radan, Milica, Popović-Nikolić, Marija, Oljačić, Slavica, Nikolić, Katarina, "The molecular basis of drug-plasma protein interaction for CNS active compounds" in 1st International Conference on Chemo and BioInformatics ICCBIKG 2021 (BOOK OF PROCEEDINGS) (2021):375-378, https://doi.org/10.46793/ICCBI21.375O . .