SYNTHESIS OF CURCUMIN DERIVATIVES CONTAINING NON-STEROIDAL ANTI-INFLAMMATORY DRUGS

Synthesis and biological evaluation of hybrid molecules combining naturally occurring antioxidant active structures with anti-inflammatory agents have been a strong trend in medicinal chemistry. This study focuses on modulating the structure of curcumin derivatives or their analogs with the use of non-steroidal anti-inflammatory drugs (NSAIDs). The combinations of curcumin, its keto-blocked derivatives, and monocarbonyl analogs with selected non-steroidal anti-inflammatory drugs (ibuprofen, naproxen) were obtained and characterized. The pyrazole, isoxazole, and benzylidene derivatives, as well as curcumin monocarbonyl analogs, were used as substrates in the reactions with selected NSAIDs. As a result of the esterification of curcumin-type diphenols, the corresponding mono- and diester-type hybrids were obtained and characterized. Moreover, in the present study, in order to verify the possibility of interactions of curcumin derivatives with the RNA binding domain of nucleocapsid phosphoprotein from SARS coronavirus 2 (PDB ID: 6VYO), we focused on the docking of the analytes to the binding pocket and analysis of amino acid interactions. The estimation of binding affinity seems to indicate that almost all synthesized compounds are able to interact with the amino acids within the cavity more effectively than referenced S-naproxen, and the most interacting amino acid residues were as follows: Arg88, Arg107, Tyr109, Gly116, Thr148, Arg149, and Asn153. Additionally, with the use of selected methods of computational chemistry (Molinspiration Cheminformatics and Osiris Property Explorer), the molecular parameters of the relevant molecules were calculated.