pKa values of aqua ligands of platinum (II) anticancer complexes: [1H, 15N] and 195Pt NMR Studies of cis- and trans- [PtCl2 (NH3) (Cyclohexylamine)]

Syntheses and NMR studies are reported of two 15N-labelled Pt(II) complexes of anticancer interest: cis-PtCl2(15NH3)(c-C6H1115NH2), a metabolite of the orally-active Pt(IV) complex cis,trans,cis-[PtCl2(acetate)2(c-C6H11NH2)(NH3), and trans-[PtCl2(15NH3)(c-C6H1115NH2), a reduction product of the active Pt(IV) complex trans,trans,trans-[PtCl2(OH)2(c-C6H11NH2). For cis-[PtCl2(15NH3)(c-C6H1115NH2), hydrolysis was faster for the chloride ligand trans to cyclohexylamine, and the pKa values determined by [1H, 15N NMR spectroscopy for the two cis monoaqua isomers were the same (6.73). The trans monoaqua complex was a stronger acid with pKa of 5.4 (determined by 195Pt NMR). For the cis diaqua complex, pKa values of 5.68 and 7.68 were determined.

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

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.

Antioxidant and cytoprotective activity of leaves of Peltiphyllum peltatum (Torr.) Engl.

The antioxidant potential of fresh leaves of Peltiphyllum peltatum (Torr.) Engl. (Saxfragaceae) was analysed by measuring scavenging potential against l,l'-diphenyl-2-picrylhydrazyl (DPPH center dot) and hydroxyl radicals (W), reducing power, inhibition of lipid peroxidation and protection of cultured cells from a lethal dose of hydrogen peroxide (H2O2). In all chemical assays used, the crude ethanolic extract of leaves of P. peltatum, which contained 21.8 +/- 1.7% (w/w, n = 3) of total phenols, was as effective as the standard antioxidant compound, rutin. Fractionation of the crude extract with solvent of increasing polarity (namely, petroleum ether, chloroform, ethyl acetate, butanol and water) led to identification of the active fractions (ethyl acetate and butanol fractions). The crude extract and its active fractions, but not rutin, protected cultured RAW 264.7 macrophages from a lethal dose Of H2O2.