Issue 48, 2009

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: [Pd2L2(μ-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(μ-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.

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

Supplementary files

Article information

Article type
Paper
Submitted
19 Jun 2009
Accepted
31 Jul 2009
First published
24 Aug 2009

Dalton Trans., 2009, 10731-10735

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

J. Spencer, A. Casini, O. Zava, R. P. Rathnam, S. K. Velhanda, M. Pfeffer, S. K. Callear, M. B. Hursthouse and P. J. Dyson, Dalton Trans., 2009, 10731 DOI: 10.1039/B912096C

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