title: Anti-Inflammatory Oxicams as Multi-donor Ligand Systems: pH- and Solvent-Dependent Coordination Modes of Meloxicam and Piroxicam to Ru and Os.
abstract: 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 [D6]DMSO/D2O (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.
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.|Department of Chemistry, University of Sargodha, Sargodha, 40100, Pakistan.
authors.forename: Farhana
authors.identifier: http://orcid.org/0000-0001-7916-2253
authors.initials: F
authors.lastname: Aman
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Muhammad
authors.identifier: http://orcid.org/0000-0002-2256-2317
authors.initials: M
authors.lastname: Hanif
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Mario
authors.identifier: http://orcid.org/0000-0001-5354-5096
authors.initials: M
authors.lastname: Kubanik
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.|Department of Chemistry, University of Sargodha, Sargodha, 40100, Pakistan.
authors.forename: Adnan
authors.identifier: http://orcid.org/0000-0002-6396-5059
authors.initials: A
authors.lastname: Ashraf
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Tilo
authors.identifier: http://orcid.org/0000-0003-4472-5807
authors.initials: T
authors.lastname: Söhnel
authors.affiliation: Auckland Cancer Society Research Centre, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Stephen M F
authors.identifier: http://orcid.org/0000-0002-5485-9211
authors.initials: SM
authors.lastname: Jamieson
authors.affiliation: Department of Chemistry, University of Sargodha, Sargodha, 40100, Pakistan.
authors.forename: Waseeq Ahmad
authors.initials: WA
authors.lastname: Siddiqui
authors.affiliation: School of Chemical Sciences, University of Auckland, Private Bag 92019, Auckland, 1142, New Zealand.
authors.forename: Christian G
authors.identifier: http://orcid.org/0000-0001-9806-0893
authors.initials: CG
authors.lastname: Hartinger
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000633:toxicity; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000633:toxicity; D018360:Crystallography, X-Ray; D045325:HCT116 Cells; D006801:Humans; D006863:Hydrogen-Ion Concentration; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D000077239:Meloxicam; D008968:Molecular Conformation; D009992:Osmium / Q000737:chemistry*; D010894:Piroxicam / Q000737:chemistry*; D012428:Ruthenium / Q000737:chemistry*; D012997:Solvents / Q000737:chemistry; D013843:Thiazines / Q000737:chemistry*; D013844:Thiazoles / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D008024:Ligands; D012997:Solvents; D013843:Thiazines; D013844:Thiazoles; D010894:Piroxicam; D009992:Osmium; D012428:Ruthenium; D000077239:Meloxicam
keywords: anticancer activity; coordination modes; osmium; oxicams; ruthenium