title: Excellent correlation between cathepsin B inhibition and cytotoxicity for a series of palladacycles.
abstract: The reaction of the five- or six-membered C,N or C,S-palladacycles [(L)PdCl](2) with PTA (1,3,5-triaza-7-phosphaadamantane) led to the monomeric complexes [(L)Pd(PTA)Cl] 6a, 6b and 7 where LH= N,N-dimethyl-1-phenylmethanamine, benzyl(methyl)sulfane or 1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one respectively. Dimeric complexes have also been synthesised: [Pd(2)L(2)(mu-dppe)Cl(2)], where LH = 1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (1a), (R)- or (S)-3-isopropyl-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (1b, 1c), [Pd(2)L(2)(mu-dppf)Cl(2)], where L= 1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (4a) or (R)-3-isopropyl-1-methyl-5-phenyl-1H-benzo[e][1,4]diazepin-2(3H)-one (4b), respectively, and dppe = 1,2-bis(diphenylphosphino)ethane, dppf = 1,1'-bis(diphenylphosphino)ferrocene. The complexes were characterised in solution, by (1)H and (31)P NMR spectroscopy, and single crystals of complexes 6b and 7 were studied in the solid state by X-ray crystallography. The palladacycles were evaluated for in vitro activity as cytotoxic agents on A2780/S cells and also as cathepsin B inhibitors, an enzyme implicated in a number of cancer related events.
authors.affiliation: School of Science, University of Greenwich at Medway, Chatham Maritime, UK ME4 4TB. j.spencer@gre.ac.uk
authors.forename: John
authors.initials: J
authors.lastname: Spencer
authors.forename: Angela
authors.initials: A
authors.lastname: Casini
authors.forename: Olivier
authors.initials: O
authors.lastname: Zava
authors.forename: Rajendra P
authors.initials: RP
authors.lastname: Rathnam
authors.forename: Santosh K
authors.initials: SK
authors.lastname: Velhanda
authors.forename: Michel
authors.initials: M
authors.lastname: Pfeffer
authors.forename: Samantha K
authors.initials: SK
authors.lastname: Callear
authors.forename: Michael B
authors.initials: MB
authors.lastname: Hursthouse
authors.forename: Paul J
authors.initials: PJ
authors.lastname: Dyson
mesh_terms: D000218:Adamantane / Q000031:analogs & derivatives / Q000737:chemistry; D002401:Cathepsin B / Q000037:antagonists & inhibitors / Q000378:metabolism*; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000737:chemistry / Q000633:toxicity*; D018360:Crystallography, X-Ray; D005296:Ferrous Compounds / Q000737:chemistry; D006801:Humans; D000075163:Metallocenes; D008968:Molecular Conformation; D009943:Organophosphorus Compounds / Q000737:chemistry; D010165:Palladium / Q000737:chemistry*; D010720:Phosphines / Q000737:chemistry
chemical_list: C501763:1,3,5-triaza-7-phosphaadamantane; D056831:Coordination Complexes; D005296:Ferrous Compounds; D000075163:Metallocenes; D009943:Organophosphorus Compounds; D010720:Phosphines; D010165:Palladium; D002401:Cathepsin B; C519379:1,1'-bis(diphenylphosphino)ferrocene; D000218:Adamantane