Human serum albumin binding of certain antimalarials
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2018
Authors
Marković, OliveraCvijetić, Ilija
Zlatović, Mario
Opsenica, Igor
Konstantinović, Jelena M.
Terzić-Jovanović, Nataša
Šolaja, Bogdan
Verbić, Tatjana
Article (Published version)
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Show full item recordAbstract
Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 degrees C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactio...ns are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved-pharmacokinetic properties and drug efficacy.
Keywords:
Aminoquinolines / Human serum albumin / Fluorescence spectroscopy / Binding affinity / Molecular docking / Stem-Volmer plotSource:
Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy, 2018, 192, 128-139Publisher:
- Oxford : Pergamon-Elsevier Science Ltd
Funding / projects:
- The synthesis of aminoquinoline-based antimalarials and botulinum neurotoxin A inhibitors (RS-MESTD-Basic Research (BR or ON)-172008)
- Rational design and synthesis of biologically active and coordination compounds and functional materials, relevant for (bio)nanotechnology (RS-MESTD-Basic Research (BR or ON)-172035)
- Reinforcement of the Faculty of Chemistry, University of Belgrade, towards becoming a Center of Excellence in the region of WB for Molecular Biotechnology and Food research (EU-FP7-256716)
- Serbian Academy of Sciences and Arts [F80]
DOI: 10.1016/j.saa.2017.10.061
ISSN: 1386-1425
PubMed: 29128746
WoS: 000424716900019
Scopus: 2-s2.0-85032915981
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Institution/Community
IHTMTY - JOUR AU - Marković, Olivera AU - Cvijetić, Ilija AU - Zlatović, Mario AU - Opsenica, Igor AU - Konstantinović, Jelena M. AU - Terzić-Jovanović, Nataša AU - Šolaja, Bogdan AU - Verbić, Tatjana PY - 2018 UR - https://cer.ihtm.bg.ac.rs/handle/123456789/2472 AB - Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 degrees C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved-pharmacokinetic properties and drug efficacy. PB - Oxford : Pergamon-Elsevier Science Ltd T2 - Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy T1 - Human serum albumin binding of certain antimalarials VL - 192 SP - 128 EP - 139 DO - 10.1016/j.saa.2017.10.061 ER -
@article{ author = "Marković, Olivera and Cvijetić, Ilija and Zlatović, Mario and Opsenica, Igor and Konstantinović, Jelena M. and Terzić-Jovanović, Nataša and Šolaja, Bogdan and Verbić, Tatjana", year = "2018", abstract = "Interactions between eight in-house synthesized aminoquinolines, along with well-known chloroquine, and human serum albumin (HSA) have been studied by fluorescence spectroscopy. The synthesized aminoquinolines, despite being structurally diverse, were found to be very potent antimalarials. Fluorescence measurements indicate that three compounds having additional thiophene or benzothiophene substructure bind more strongly to HSA than other studied compounds. Competitive binding experiments indicate that these three compounds bind significantly stronger to warfarin compared to diazepam binding site. Fluorescence quenching at three temperatures (20, 25, and 37 degrees C) was analyzed using classical Stern-Volmer equation, and a static quenching mechanism was proposed. The enthalpy and entropy changes upon sulphur-containing compound-HSA interactions were calculated using Van't Hoff equation. Positive values of enthalpy and entropy changes indicate that non-specific, hydrophobic interactions are the main contributors to HSA-compound interaction. Molecular docking and calculated lipophilicity descriptors indicate the same, pointing out that the increased lipophilicity of sulphur-containing compounds might be a reason for their better binding to HSA. Obtained results might contribute to design of novel derivatives with improved-pharmacokinetic properties and drug efficacy.", publisher = "Oxford : Pergamon-Elsevier Science Ltd", journal = "Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy", title = "Human serum albumin binding of certain antimalarials", volume = "192", pages = "128-139", doi = "10.1016/j.saa.2017.10.061" }
Marković, O., Cvijetić, I., Zlatović, M., Opsenica, I., Konstantinović, J. M., Terzić-Jovanović, N., Šolaja, B.,& Verbić, T.. (2018). Human serum albumin binding of certain antimalarials. in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy Oxford : Pergamon-Elsevier Science Ltd., 192, 128-139. https://doi.org/10.1016/j.saa.2017.10.061
Marković O, Cvijetić I, Zlatović M, Opsenica I, Konstantinović JM, Terzić-Jovanović N, Šolaja B, Verbić T. Human serum albumin binding of certain antimalarials. in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy. 2018;192:128-139. doi:10.1016/j.saa.2017.10.061 .
Marković, Olivera, Cvijetić, Ilija, Zlatović, Mario, Opsenica, Igor, Konstantinović, Jelena M., Terzić-Jovanović, Nataša, Šolaja, Bogdan, Verbić, Tatjana, "Human serum albumin binding of certain antimalarials" in Spectrochimica Acta Part A-Molecular and Biomolecular Spectroscopy, 192 (2018):128-139, https://doi.org/10.1016/j.saa.2017.10.061 . .