doiSerbia

Solvent effects on the absorption spectra of potentially pharmacologically active 5-alkyl-5-arylhydantoins: A structure-property relationship study

Hmuda Sleem F. (Department of Organic Chemistry, Faculty of Technology and Metallurgy, Belgrade)
Banjac Nebojša R. (Department of Organic Chemistry, Faculty of Technology and Metallurgy, Belgrade)
Trišović Nemanja P. (Department of Organic Chemistry, Faculty of Technology and Metallurgy, Belgrade)
Božić Bojan Đ. (Department of Organic Chemistry, Faculty of Technology and Metallurgy, Belgrade)
Valentić Nataša V. (Department of Organic Chemistry, Faculty of Technology and Metallurgy, Belgrade)
Ušćumlić Gordana S. (Department of Organic Chemistry, Faculty of Technology and Metallurgy, Belgrade)

To obtain an insight into the interactions of potential anticonvulsant drugs with their surrounding, two series of 5-methyl-5-aryl- and 5-ethyl-5-arylhydantoins were synthesized and their absorption spectra were recorded in the region from 200 to 400 nm in a set of selected solvents. The effects of solvent dipolarity/polarizability and solvent-solute hydrogen bonding interactions on the absorption maxima shifts were analyzed by means of the linear solvation energy relationship (LSER) concept of Kamlet and Taft. The ratio of the contributions of specific and nonspecific solvent-solute interactions were correlated with the corresponding ADME properties of the studied compounds. The correlation equations were combined with different physicochemical parameters to generate new equations, which demonstrate the reasonable relationships between solvent-solute interactions and the structure-activity parameters.

Keywords: hydantoin derivatives, Kamlet-Taft Equation, human intestinal absorption, lipophilicity, , binding affinity

Projekat Ministarstva nauke Republike Srbije, br. 172013