Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands
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2019
Authors
Šegan, Sandra
Penjišević, Jelena

Šukalović, Vladimir

Andrić, Deana

Milojković-Opsenica, Dušanka

Kostić Rajačić, Slađana

Article (Published version)

Elsevier
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Show full item recordAbstract
Reversed-phase thin-layer chromatography and micellar thin-layer chromatography were used in order to investigate retention behaviour and to determine lipophilicity of series of 2(methoxy)phenylpiperazine dopamine D2 ligands with different size, shape and rigidity. The retention mechanism was discussed. The lipophilicity parameters obtained in conventional reversed-phase systems expressed as RM0 and C0, as well as RM values
determined in microemulsion reversed-phase systems were correlated with in silico determined lipophilicity values. In silico pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands revealed the importance of experimentally determined lipophilicity values besides the molecular weight, on the blood–brain barrier permeability process. Also, the experimentally determined lipophilicity was found as a very important factor in plasma protein binding process of 2-(methoxy)phenylpiperazine dopamine D2 ligands. Besides, the Lipinski's rule of five indic...ates that examined ligands satisfy the criterion of drug-like molecules. The principal component analysis was performed on the experimentally determined and calculated lipophilicity values as well on the molecular descriptors which describe the pharmacokinetic properties in order to provide basic insights into similarities among the studied ligands.
Keywords:
2-(Methoxy)phenylpiperazine dopamine D2 ligands / Reversed-phase thin-layer chromatography (RPTLC) / Microemulsion thin-layer chromatography (METLC) / Lipophilicity / Blood–brain barrier (BBB) permeability / Protein binding capacity (QPlogKhsa)Source:
Journal of Chromatography B, 2019, 1124, 146-153Publisher:
- Elsevier
Funding / projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-172008)
- Structure-activity relationship of newly synthesized biological active compound (RS-172032)
DOI: 10.1016/j.jchromb.2019.06.006
ISSN: 1570-0232
WoS: 000477685600015
Scopus: 2-s2.0-85067083868
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IHTMTY - JOUR AU - Šegan, Sandra AU - Penjišević, Jelena AU - Šukalović, Vladimir AU - Andrić, Deana AU - Milojković-Opsenica, Dušanka AU - Kostić Rajačić, Slađana PY - 2019 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2991 AB - Reversed-phase thin-layer chromatography and micellar thin-layer chromatography were used in order to investigate retention behaviour and to determine lipophilicity of series of 2(methoxy)phenylpiperazine dopamine D2 ligands with different size, shape and rigidity. The retention mechanism was discussed. The lipophilicity parameters obtained in conventional reversed-phase systems expressed as RM0 and C0, as well as RM values determined in microemulsion reversed-phase systems were correlated with in silico determined lipophilicity values. In silico pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands revealed the importance of experimentally determined lipophilicity values besides the molecular weight, on the blood–brain barrier permeability process. Also, the experimentally determined lipophilicity was found as a very important factor in plasma protein binding process of 2-(methoxy)phenylpiperazine dopamine D2 ligands. Besides, the Lipinski's rule of five indicates that examined ligands satisfy the criterion of drug-like molecules. The principal component analysis was performed on the experimentally determined and calculated lipophilicity values as well on the molecular descriptors which describe the pharmacokinetic properties in order to provide basic insights into similarities among the studied ligands. PB - Elsevier T2 - Journal of Chromatography B T1 - Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands VL - 1124 SP - 146 EP - 153 DO - 10.1016/j.jchromb.2019.06.006 ER -
@article{ author = "Šegan, Sandra and Penjišević, Jelena and Šukalović, Vladimir and Andrić, Deana and Milojković-Opsenica, Dušanka and Kostić Rajačić, Slađana", year = "2019", abstract = "Reversed-phase thin-layer chromatography and micellar thin-layer chromatography were used in order to investigate retention behaviour and to determine lipophilicity of series of 2(methoxy)phenylpiperazine dopamine D2 ligands with different size, shape and rigidity. The retention mechanism was discussed. The lipophilicity parameters obtained in conventional reversed-phase systems expressed as RM0 and C0, as well as RM values determined in microemulsion reversed-phase systems were correlated with in silico determined lipophilicity values. In silico pharmacokinetic properties of 2-(methoxy)phenylpiperazine dopamine D2 ligands revealed the importance of experimentally determined lipophilicity values besides the molecular weight, on the blood–brain barrier permeability process. Also, the experimentally determined lipophilicity was found as a very important factor in plasma protein binding process of 2-(methoxy)phenylpiperazine dopamine D2 ligands. Besides, the Lipinski's rule of five indicates that examined ligands satisfy the criterion of drug-like molecules. The principal component analysis was performed on the experimentally determined and calculated lipophilicity values as well on the molecular descriptors which describe the pharmacokinetic properties in order to provide basic insights into similarities among the studied ligands.", publisher = "Elsevier", journal = "Journal of Chromatography B", title = "Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands", volume = "1124", pages = "146-153", doi = "10.1016/j.jchromb.2019.06.006" }
Šegan, S., Penjišević, J., Šukalović, V., Andrić, D., Milojković-Opsenica, D.,& Kostić Rajačić, S.. (2019). Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands. in Journal of Chromatography B Elsevier., 1124, 146-153. https://doi.org/10.1016/j.jchromb.2019.06.006
Šegan S, Penjišević J, Šukalović V, Andrić D, Milojković-Opsenica D, Kostić Rajačić S. Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands. in Journal of Chromatography B. 2019;1124:146-153. doi:10.1016/j.jchromb.2019.06.006 .
Šegan, Sandra, Penjišević, Jelena, Šukalović, Vladimir, Andrić, Deana, Milojković-Opsenica, Dušanka, Kostić Rajačić, Slađana, "Investigation of lipophilicity and pharmacokinetic properties of 2-(methoxy) phenylpiperazine dopamine D2 ligands" in Journal of Chromatography B, 1124 (2019):146-153, https://doi.org/10.1016/j.jchromb.2019.06.006 . .