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. RuII(arene) complexes with methyl ester derivatives of the oxicam scaffold were prepared and characterized by standard methods and crystallographically. The organoruthenium compounds formed from RuII(η6-p-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 in vitro assay. The cytotoxicity was found strongly dependent on the lipophilicity of the compound, as was shown through correlation with log k w and clog P values of the ligands. The most lipophilic compound [chlorido(methyl 4-oxido-2-benzyl-2H-1,2-benzothiazine-3-carboxylate-1,1-dioxide)(η6-p-cymene)ruthenium(II)] was the most active in the cell assays, with an IC50 of 80 μM in HCT116 cells.

Key indicators: single-crystal X-ray study; T = 173 K; mean (C-C) = 0.002 Å; R factor = 0.033; wR factor = 0.089; data-to-parameter ratio = 15.4.The title compound, C 7 H 7 NO 4 S, contains an extensive hydrogen-bonded network involving three intermolecular and three intramolecular interactions that stabilize the structure.

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The nitrogen- and sulfur-containing 1,2-benzothiazines meloxicam and piroxicam are widely used as nonsteroidal anti-inflammatory drugs. Intrigued by the presence of multiple donor atoms and therefore potentially rich coordination chemistry, we prepared a series of organometallic Ru and Os compounds with meloxicam and piroxicam featuring either as mono- or bidentate ligand systems. The choice of the solvent and the pH value was identified as the critical parameter to achieve selectively mono- or bidentate coordination. The coordination modes were confirmed experimentally by NMR spectroscopy and single crystal X-ray diffraction analysis. Using DFT calculations, it was established that complexes in which meloxicam acts as a bidentate N,O donor are energetically more favorable than coordination as O,O and S,O donor systems. Since meloxicam and piroxicam derivatives have shown anticancer activity in the past, we aimed to compare the complexes with mono- and bidentate ligands on their in vitro anticancer activity. However, stability studies revealed that only the latter complexes were stable in [D ]DMSO/D O (5:95) and therefore no direct comparisons could be made. The meloxicam complexes 1 and 2 showed moderate cytotoxicity, whereas the piroxicam derivatives 5 and 6 were hardly active against the utilized cell lines.

A new method for description of molecular networks and packings is proposed and implemented into the program package TOPOS.