Retention behavior analysis and lipophilicity assessment of COX-2/5-LOX inhibitors using RP-HPLC

Dual COX-2/5-LOX inhibitors represent a promising strategy for safer and more effective treatment of chronic inflammation-related diseases. Building on our previous work, a set of thirteen structurally diverse compounds ( 1–13 ) that act as inhibitors of these enzymes was analyzed to investigate their lipophilicity and retention behaviour using reversed-phase high-performance liquid chromatography (RP-HPLC). Some of these compounds were designed by introducing polar pharmacophores into the structure of conventional COX inhibitors. Therefore, it is highly important to assess the impact of these structural modifications on lipophilicity. Among several chromatographic systems tested, the C18 column with an acetonitrile/phosphate buffer mobile phase was identified as optimal, showing the strongest correlation between the experimental retention data and the calculated lipophilicity ( logD ). The retention parameter logkw proved to be the most reliable indicator of lipophilicity. It ranged from 1.40 to 3.21, with the highest values for bulky di- tert -butylphenols and the lowest for polar hydroxamic/urea derivatives. PCA analysis highlighted five molecular descriptors with the highest influence on retention ( CATS2D_05_AL, CATS2D_02_AA, MaxssNH, NssNH , and P_VSA_charge_6 ). Interpretation of these descriptors could be used as a starting point for further chemical modifications of tested compounds.