New Oxicam Derivatives-Studies of Membrane Interactions, Cytotoxicity, Cyclooxygenase Inhibition and Molecular...

Oxicam derivatives, a class of nonsteroidal anti-inflammatory drugs (NSAIDs), are important scaffolds for developing biologically active compounds. In this study, arylpiperazine oxicam derivatives (PR24-PR50) were examined for membrane interactions, cytotoxic activity, cyclooxygenase inhibition, and potential binding to COX-2 protein. Membrane interactions were examined using differential scanning calorimetry (DSC) in phospholipid bilayers formed from 1,2-dimyristoyl-sn-glycero-3-phosphocholine (DMPC). All compounds altered the thermotropic properties of the lipid bilayer, showing concentration-dependent decreases in phase transition temperature, indicating incorporation to bilayer and partial disruption of lipid organization. Cytotoxicity, assessed using the MTT assay in breast cancer (MCF-7, MCF-7/DX), colorectal cancer (LOVO, LOVO/DX), and normal V79 cell lines, showed moderate effects, particularly against colorectal cancer cells. Cyclooxygenase inhibition was rather weak, with IC₅₀ values in the high micromolar range, indicating limited anti-inflammatory potential compared with reference COX inhibitors, although docking studies suggested possible interactions with the COX-2 active site. The obtained results indicate that the biological activity of the arylpiperazine oxicam derivatives is primarily associated with cytotoxicity and membrane effects rather than COX inhibition. These limitations should be considered in the design of future membrane-targeted bioactive compounds.