Human serum albumin binding of certain antimalarials
Autori
Marković, Olivera S.Cvijetić, Ilija
Zlatović, Mario
Opsenica, Igor
Terzić-Jovanović, Nataša
Šolaja, Bogdan A.
Verbić, Tatjana
Konferencijski prilog (Objavljena verzija)
Metapodaci
Prikaz svih podataka o dokumentuApstrakt
Tested compounds, previously synthesized, are derivatives of chloroquine, drug commonly
used in the treatment and prevention of malaria. Human serum albumin (HSA) has the role in
transport of endogenous (fatty acids, hormones, bile acids, amino acids) and exogenous
compounds (drug molecules and nutrients). Interaction between tested compounds and HSA
has been studied by fluorescence spectroscopy in phosphate buffered saline (1× PBS, pH 7.4)
[1]. Results show that among tested compounds, all positively charged at pH 7.4, derivatives
with thiophene substructure bind to HSA. Molecular docking studies were used to determine
HSA–compound binding mode.
Fluorescence quenching data were processed using Stern-Volmer (S-V) equation [2]. Almost
linear S-V plot for binding of 1 to HSA (Fig. 1a) indicates single type of quenching mechanism.
Results show that Ksv decreases (20C: (2.60±0.07)×105 M
-1
; 25C: (2.33±0.07)×105 M
-1 and
37C: (2.18±0.08)×105 M
-1
) as temperatu...re increases indicating static quenching mechanism.
Downward curvature in S-V plots of 2 and 3 (Fig. 1b and 1c) indicates that tryptophan residues
are not fully accessible to the drug and that dynamic quenching dominates over static. Fraction
of tryptophan residues that are buried and inaccessible to the quencher and effective
quenching constants can be determined by modified S-V equation. The effective quenching
constant for 2 and 3 increases as temperature increases, this is another indication that dynamic
quenching process is dominant in binding of 2 and 3 to HSA. Effective quenching constants of
all three compounds are in the order of 10 5 M-1, meaning that these compounds can be
effectively carried and stored by HSA in the human body.
Izvor:
4th World Conference on Physico-Chemical Methods in Drug Discovery and Development, Red Island, Croatia, September 21-24, 2015, 2015, 67-67Finansiranje / projekti:
- Sinteza aminohinolina i njihovih derivata kao antimalarika i inhibitora botulinum neurotoksina A (RS-MESTD-Basic Research (BR or ON)-172008)
- 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)
Kolekcije
Institucija/grupa
Hemijski fakultet / Faculty of ChemistryTY - CONF AU - Marković, Olivera S. AU - Cvijetić, Ilija AU - Zlatović, Mario AU - Opsenica, Igor AU - Terzić-Jovanović, Nataša AU - Šolaja, Bogdan A. AU - Verbić, Tatjana PY - 2015 UR - http://cherry.chem.bg.ac.rs/handle/123456789/5323 AB - Tested compounds, previously synthesized, are derivatives of chloroquine, drug commonly used in the treatment and prevention of malaria. Human serum albumin (HSA) has the role in transport of endogenous (fatty acids, hormones, bile acids, amino acids) and exogenous compounds (drug molecules and nutrients). Interaction between tested compounds and HSA has been studied by fluorescence spectroscopy in phosphate buffered saline (1× PBS, pH 7.4) [1]. Results show that among tested compounds, all positively charged at pH 7.4, derivatives with thiophene substructure bind to HSA. Molecular docking studies were used to determine HSA–compound binding mode. Fluorescence quenching data were processed using Stern-Volmer (S-V) equation [2]. Almost linear S-V plot for binding of 1 to HSA (Fig. 1a) indicates single type of quenching mechanism. Results show that Ksv decreases (20C: (2.60±0.07)×105 M -1 ; 25C: (2.33±0.07)×105 M -1 and 37C: (2.18±0.08)×105 M -1 ) as temperature increases indicating static quenching mechanism. Downward curvature in S-V plots of 2 and 3 (Fig. 1b and 1c) indicates that tryptophan residues are not fully accessible to the drug and that dynamic quenching dominates over static. Fraction of tryptophan residues that are buried and inaccessible to the quencher and effective quenching constants can be determined by modified S-V equation. The effective quenching constant for 2 and 3 increases as temperature increases, this is another indication that dynamic quenching process is dominant in binding of 2 and 3 to HSA. Effective quenching constants of all three compounds are in the order of 10 5 M-1, meaning that these compounds can be effectively carried and stored by HSA in the human body. C3 - 4th World Conference on Physico-Chemical Methods in Drug Discovery and Development, Red Island, Croatia, September 21-24, 2015 T1 - Human serum albumin binding of certain antimalarials SP - 67 EP - 67 UR - https://hdl.handle.net/21.15107/rcub_cherry_5323 ER -
@conference{ author = "Marković, Olivera S. and Cvijetić, Ilija and Zlatović, Mario and Opsenica, Igor and Terzić-Jovanović, Nataša and Šolaja, Bogdan A. and Verbić, Tatjana", year = "2015", abstract = "Tested compounds, previously synthesized, are derivatives of chloroquine, drug commonly used in the treatment and prevention of malaria. Human serum albumin (HSA) has the role in transport of endogenous (fatty acids, hormones, bile acids, amino acids) and exogenous compounds (drug molecules and nutrients). Interaction between tested compounds and HSA has been studied by fluorescence spectroscopy in phosphate buffered saline (1× PBS, pH 7.4) [1]. Results show that among tested compounds, all positively charged at pH 7.4, derivatives with thiophene substructure bind to HSA. Molecular docking studies were used to determine HSA–compound binding mode. Fluorescence quenching data were processed using Stern-Volmer (S-V) equation [2]. Almost linear S-V plot for binding of 1 to HSA (Fig. 1a) indicates single type of quenching mechanism. Results show that Ksv decreases (20C: (2.60±0.07)×105 M -1 ; 25C: (2.33±0.07)×105 M -1 and 37C: (2.18±0.08)×105 M -1 ) as temperature increases indicating static quenching mechanism. Downward curvature in S-V plots of 2 and 3 (Fig. 1b and 1c) indicates that tryptophan residues are not fully accessible to the drug and that dynamic quenching dominates over static. Fraction of tryptophan residues that are buried and inaccessible to the quencher and effective quenching constants can be determined by modified S-V equation. The effective quenching constant for 2 and 3 increases as temperature increases, this is another indication that dynamic quenching process is dominant in binding of 2 and 3 to HSA. Effective quenching constants of all three compounds are in the order of 10 5 M-1, meaning that these compounds can be effectively carried and stored by HSA in the human body.", journal = "4th World Conference on Physico-Chemical Methods in Drug Discovery and Development, Red Island, Croatia, September 21-24, 2015", title = "Human serum albumin binding of certain antimalarials", pages = "67-67", url = "https://hdl.handle.net/21.15107/rcub_cherry_5323" }
Marković, O. S., Cvijetić, I., Zlatović, M., Opsenica, I., Terzić-Jovanović, N., Šolaja, B. A.,& Verbić, T.. (2015). Human serum albumin binding of certain antimalarials. in 4th World Conference on Physico-Chemical Methods in Drug Discovery and Development, Red Island, Croatia, September 21-24, 2015, 67-67. https://hdl.handle.net/21.15107/rcub_cherry_5323
Marković OS, Cvijetić I, Zlatović M, Opsenica I, Terzić-Jovanović N, Šolaja BA, Verbić T. Human serum albumin binding of certain antimalarials. in 4th World Conference on Physico-Chemical Methods in Drug Discovery and Development, Red Island, Croatia, September 21-24, 2015. 2015;:67-67. https://hdl.handle.net/21.15107/rcub_cherry_5323 .
Marković, Olivera S., Cvijetić, Ilija, Zlatović, Mario, Opsenica, Igor, Terzić-Jovanović, Nataša, Šolaja, Bogdan A., Verbić, Tatjana, "Human serum albumin binding of certain antimalarials" in 4th World Conference on Physico-Chemical Methods in Drug Discovery and Development, Red Island, Croatia, September 21-24, 2015 (2015):67-67, https://hdl.handle.net/21.15107/rcub_cherry_5323 .