Akademik Veri Yönetim Sistemi
12th Aegean Analytical Chemistry Days 2023, İstanbul, Türkiye, 19 - 22 Ekim 2023, ss.184-185, (Özet Bildiri)
It is inevitable for drugs to interact with hemoglobin (Hb), a blood protein, while being absorbed into the body and transported to target tissues through the blood. In this interaction, drug molecules act as ligands and form a complex structure by binding to hemoglobin. Thanks to this complex structure, hemoglobin can act as a natural drug carrier system [1]. Examining the interactions of drug candidates with hemoglobin, one of the drug carrier systems in the blood, is important in terms of pharmacology and pharmacokinetics. Hemoglobin-drug bindings can be elucidated by spectroscopic methods due to the fluorescence properties of Hb. Coumarins and their derivatives are natural compounds belonging to the group of secondary metabolites found in plants, and they exhibit a wide range of pharmacological effects. They are members of a class of compounds called benzopyrones, which are formed chemically by fusing a benzene ring with an α-pyrone ring [2]. Biscoumarins are dimeric coumarin derivatives linked by a bridge such as methylene, ethylene etc. They have also been observed to have broad biochemical and pharmaceutical properties [3]. The biscoumarin derivatives B1 (6,6'-methylenebis(3- (3,4-dihydroxyphenyl)-2H-chromen-2-one) and B2 (6,6'-methylenebis(3-(3,4-diacetoxyphenyl)-2Hchromen-2-one), whose binding to hemoglobin we examined, were also previously evaluated for their inhibitory effects on the monoamine oxidase (MAO) enzyme activity by our group. It was determined that B1 was selective for MAO-A and B2 for MAO-B. In our study, the binding and transport of previously synthesized and characterized biscoumarin derivatives with MAO inhibitory activity to bovine hemoglobin (BHB) were investigated by in silico and in vitro methods. Firstly, in silico molecular docking calculations (ligand binding energies, ligand efficiency values, and interaction types with amino acid residues in the active site) of the ligands and hemoglobin were carried out. Then the binding of the compounds to hemoglobin was examined in vitro using multi-spectroscopic methods such as UV-vis absorbance, fluorescence, and synchronized fluorescence. As a result of the studies, changes in the absorbance of BHB, fluorescence intensity, and microenvironment of tyrosine and tryptophan residues, as well as quenching mechanisms, binding constants, and the number of binding sites, were determined.