Hydantoin derivates are a well-known class of antiepileptic drugs used in the treatment of epilepsy for decades. Besides anticonvulsive hydantoins shows and other types of activities, such as antiarrhythmic, antimicrobial agents, and skeletal muscle relaxants [1]. Similarly, spirohydantoins represent a pharmacologically activities important class of compounds with a wide range of activities [2].
One of the most important properties closely related to the biological activity is lipophilicity. Lipophilicity refers to the tendency of a compound to partition between a lipophilic organic phase and a polar aqueous phase. In drug development lipophilicity of a compound is represented either as partition coefficient, log P, or distribution coefficient, log D. Lipophilicity is responsible for pharmacokinetics, and hence important for further development of potentially active compounds [3]. In addition to lipophilicity, adequate bioavailability is one of the crucial properties of drug candidates. Recognition of potentially biologically active compounds can be supported by the use of very simple rules, such as the Lipinski Rule of five [4]. The rule describes molecular properties important for a drug's pharmacokinetics and includes absorption, distribution, metabolism, excretion, and toxicity (ADMET).
The goal of this study was to determine chromatographic lipophilicity parameters of cycloalkylspiro-5-hidantoins using different mobile phase and to find the correlation between retention, log P as well as in silico ADMET descriptors of the investigated spirohydantoins. Lipinski rule of five is carrying out to verify if investigated spirohydantoins exhibit good (theoretical) oral bioavailability. To estimate the potential acute toxicity of the investigate spirohydantoin derivatives, their effective concentrations, EC50, on the selected test organisms have been calculated.
The lipophilicity of 21 new spirohydantoin derivatives was determined using reversed-phase thin-layer chromatography on C-18 modified silica gel and a two-component aqueous mobile phase. As a modifier of the mobile phase were used different organic solvents (ethanol, n-propanol, i-propanol, or t-butanol). Also, lipophilicity was calculated by using the relevant software packages. The calculated partition coefficient, log P, as a standard measure of lipophilicity are compared with experimentally determined lipophilicity.