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Dalton Transactions

The international journal for inorganic, organometallic and bioinorganic chemistry



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Dalton Trans., 2009, 10731 - 10735, DOI: 10.1039/b912096c

Excellent correlation between cathepsin B inhibition and cytotoxicity for a series of palladacycles

John Spencer, Angela Casini, Olivier Zava, Rajendra P. Rathnam, Santosh K. Velhanda, Michel Pfeffer, Samantha K. Callear, Michael B. Hursthouse and Paul J. Dyson

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: [Pd2L2(-dppe)Cl2], 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), [Pd2L2(-dppf)Cl2], 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 1H and 31P 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.

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