Oxicams as Bioactive Ligand System in Coordination Complexes and Their Biological Applications

Oxicam is a class of non-steroidal anti-inflammatory drugs (NSAIDs) that exhibits structural similarities to the enolic acid of 4-hydroxy-1,2-benzothiazine carboxamides. The oxicam derivatives have the ability to coordinate with different metal ions in a monodentate and bidentate fashion. The choice of ligand and reaction conditions played a key role for the synthesis of desired oxicam-based metal complexes. In this review, oxicam-based Mn(II), Fe(II), Co(II), Ni(II), Cu(II) and Zn(II) transition metal complexes are being discussed. In all these complexes, the oxicams acted as N,O-coordinating chelators and stabilized metal complexes by forming six-membered ring systems. The coordination geometries of the metal complexes are dependent on the oxicam derivatives, co-ligands as well as selected metal ions. The octahedral, square pyramidal, square planar and tetrahedral geometries are concluded with the supported by electronic transitions and magnetic data of the oxicam functionalized metal complexes. The antibacterial, anticancer, and DNA interaction of the oxicam-based metal complexes have also been discussed. The antibacterial and anticancer activities indicated that some metal complexes are more potent as compared to free ligands. The DNA binding studies confirmed that the metal complexes interact with DNA via major grooves.</p

Anticancer Ruthenium(η⁶‑<i>p</i>‑cymene) Complexes of Nonsteroidal Anti-inflammatory Drug Derivatives

Oxicams are a versatile family of heterocyclic compounds, and the two representatives meloxicam and piroxicam are widely used drugs for the treatment of a variety of inflammatory and rheumatic diseases in humans. As cancer-associated inflammation is known to occur in carcinogenesis, we aimed to combine compounds carrying bioactive oxicam moieties with ruthenium­(arene) fragments, known for anticancer activity. Ru^II(arene) complexes with methyl ester derivatives of the oxicam scaffold were prepared and characterized by standard methods and crystallographically. The organoruthenium compounds formed from Ru^II(η⁶-<i>p</i>-cymene) chlorido moieties and oxicam-based ligands were subjected to bioanalytical investigations to establish their physicochemical properties with regard to stability in DMSO and water as well as reactivity toward the amino acids l-histidine (His), l-methionine (Met), and l-cysteine (Cys) and the DNA model compound guanosine 5′-monophosphate (5′-GMP). The compounds hydrolyzed rapidly in water to give the respective aqua complexes, formed amino acid complexes with Met and His, but decompose with Cys, while interaction with 5′-GMP was through its phosphate residue. The anticancer activity of the complexes against the colon carcinoma HCT116 and breast cancer MDA MB 231 cancer cell lines was established using an <i>in vitro</i> assay. The cytotoxicity was found strongly dependent on the lipophilicity of the compound, as was shown through correlation with log<i> k</i>_w and clog<i> P</i> values of the ligands. The most lipophilic compound [chlorido­(methyl 4-oxido-2-benzyl-2<i>H</i>-1,2-benzothiazine-3-carboxylate-1,1-dioxide)­(η⁶-<i>p</i>-cymene)­ruthenium­(II)] was the most active in the cell assays, with an IC₅₀ of 80 μM in HCT116 cells