Characterization of Sulfonylureas’ ADME Properties Using Biomimetic Chromatography and Computational Procedures (CROSBI ID 727249)
Prilog sa skupa u zborniku | sažetak izlaganja sa skupa | domaća recenzija
Podaci o odgovornosti
Rajić, Martina ; Jeličić, Mario-Livio ; Cindro, Nikola ; Kovačić, Jelena ; Amidžić Klarić, Daniela ; Mornar Turk, Ana
engleski
Characterization of Sulfonylureas’ ADME Properties Using Biomimetic Chromatography and Computational Procedures
Sulfonylureas are the oldest class of oral antidiabetic medication used to treat type 2 diabetes. There are two generations of sulfonylureas, and both are equally effective in lowering glucose concentration in the blood. Still, they differ in pharmacological properties such as absorption, metabolism, elimination, and dosing. Therefore, modern and advanced methods are being researched daily to determine the pharmacological properties of the new potential drugs. One of the latest methods is biomimetic chromatography which uses columns that mimic biological conditions and computer (in silico) methods that predict various ADME (Adsorption, Distribution, Metabolism, Excretion) and QSPR (Quantitative Structure- Property Relationship) parameters. The present study was designed to gain insight into the ADME parameters such as lipophilicity, solubility, phospholipophilicity, protein plasma binding, oral bioavailability, distribution coefficient, gastrointestinal absorption, and compliance with Lipinski's "rule of five" of three sulfonylureas (N- methylcarbamoyl)-4- methylbenzenesulfoamide, (N- benzylcarbamoyl)-4- methylbenzenesulfonamide, and 1, 1’- trimethylenebis[3-(p-tolylsulfonyl)-urea] by using HPLC biomimetic chromatography and various computer programs for prediction of stated properties. More precisely, our study focused on determining the lipophilicity and phospholipopilicity of three sulfonylureas using C18 (octadecylsilane) chromatographic and Immobilized Artificial Membrane (IAM) columns. Chromatographic columns with human serum albumin (HSA) and α-1-acid glycoprotein (AGP) were used to characterize plasma proteins binding. Various free and commercially available programs were used to predict the ADME properties of stated compounds. For the parameters for which it was possible, the experimentally obtained values were correlated with the calculated ones. The experimental results showed that all three sulfonylureas are lipophilic, interact with phospholipids, and bind to HSA and AGP plasma proteins. Furthermore, a high coefficient of determination (R2>0.9) was obtained for most of the calculated parameters with experimentally determined parameters. Therefore, obtained calculated and experimental values' results would benefit further research of the analyzed sulfonylureas as potential drugs.
ADME, biomimetic chromatography, computational procedures, drugs, in silico, sulfonylurea, QSPR
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Podaci o prilogu
110-110.
2022.
objavljeno
Podaci o matičnoj publikaciji
SiC2022 Book of Abstracts
Kassal, Petar ; Meštrović, Ernest ; Namjesnik, Danijel ; Ribić, Rosana ; Šekutor, Marina ; Tomišić ; Vladislav Tomišić, Usenik, Andrea
Sveti Martin na Muri:
Podaci o skupu
International Conference Solutions in Chemistry 2022
poster
08.11.2022-11.11.2022
Sveti Martin na Muri, Hrvatska
Povezanost rada
Farmacija, Interdisciplinarne prirodne znanosti, Kemija, Računarstvo, Temeljne medicinske znanosti