Mode of binding, kinetic and thermodynamic properties of a lipid-like drug (Fingolimod) interacting with Human Serum Albumin

Mode of binding, kinetic and thermodynamic properties of a lipid-like drug (Fingolimod) interacting with Human Serum Albumin Samira Gholizadeh Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran http://orcid.org/0000-0001-6705-1150 Hossein Haghaei Faculty of Nutrition and Food Sciences, Tabriz University of Medical Sciences, Tabriz, Iran Hosna Karami Pharmaceutical Analysis Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Somaieh Soltani Pharmacy Faculty, Tabriz University of Medical Sciences, Tabriz, Iran Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran http://orcid.org/0000-0002-0102-2960 Mostafa Zakariazadeh Departement of Biology, Faculty of Sciences, Payame Noor University, PO.box 19395-3697, Tehran, Iran Javad Shokri Pharmacy Faculty, Tabriz University of Medical Sciences, Tabriz, Iran

Introduction: Fingolimod is a drug that is used to treat multiple sclerosis (MS). It has pH-dependent solubility and low solubility when buffering agents are present. Multi-spectroscopic and molecular modeling methods were used to investigate the molecular mechanism of Fingolimod interaction with human serum albumin (HSA), and the resulting data were fitted to the appropriate models to investigate the molecular mechanism of interaction, binding constant, and thermodynamic properties. Methods: The interaction of Fingolimod with HSA was investigated in a NaCl aqueous solution (0.1 mM). The working solutions had a pH of 6.5. Data was collected using UV-vis, fluorescence quenching titrations, FTIR, and molecular modeling methods. Results: According to the results of the fluorescence quenching titrations, the quenching mechanism is static. The apparent binding constant value (KA = 4.26×103) showed that Fingolimod is a moderate HSA binder. The reduction of the KA at higher temperatures could be a result of protein unfolding. Hydrogen bonding and van der Waals interactions are the main contributors to Fingolimod-HSA complex formation. FTIR and CD characterizations suggested a slight decrease in the α-helix and β-sheets of the secondary structure of HSA due to Fingolimod binding. Fingolimod binds to the binding site II, while a smaller tendency to the binding site I was observed as well. The results of the site marker competitive experiment and the thermodynamic studies agreed with the results of the molecular docking. Conclusion: The pharmacokinetic properties of fingolimod can be influenced by its HSA binding. In addition, considering its mild interaction, site II binding drugs are likely to compete. The methodology described here may be used to investigate the molecular mechanism of HSA interaction with lipid-like drugs with low aqueous solubility or pH-dependent solubility.
11 27 2022 1 10.34172/crossmark_policy bi.tbzmed.ac.ir false Tabriz University of Medical Sciences Tabriz University of Medical Sciences 2020-08-24 2021-06-29 2022-11-27 10.34172/bi.2022.23383 20230221015331 https://bi.tbzmed.ac.ir/Inpress/bi-23383 https://bi.tbzmed.ac.ir/Inpress/bi-23383.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23383.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23383.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23383.pdf https://bi.tbzmed.ac.ir/Inpress/bi-23383.pdf