Synthesis of a 1,4-benzodiazepine containing palladacycle with in vitro anticancer and cathepsin B activity

Abstract

The reaction of the five-membered C,N-palladacycle [(L)PdCl](2), where LH = 1-methyl-5-phenyl-1H-1,4-benzodiazepin-2(3H)-one, with 1,2-ethanebis(diphenylphosphine), dppe, leads to the formation of the bridged palladacycle. [Pd(2)L(2)(mu-dppe)Cl(2)] 3, which was characterised in solution by (1)H and (31)P NMR spectroscopy and in the solid state by X-ray crystallography. Complex 3 was tested in vitro against a number of cell lines. For example, it inhibited K562 leukaemia cells with an IC(50) value of 4.3 microM (1 h exposure) and displayed cathepsin B inhibitory action with an IC(50) value of 3 microM.

Mono- and binuclear orthopalladated complexes of phosphorus ylides containing nitrogen, phosphorus or bridging diphosphine ligands: Self-assembly, theoretical calculations and comparative catalytic activity

“…The 1 H NMR spectra of complexes with pyridine derivatives (1b, 1c, 1d and 2b, 2c) show the resonances attributed to the H 6 of the C 6 H 4 , shifted strongly to upfield. This is also observed in the other complexes [34,38] according to the anisotropic shielding of this proton due to the vicinity to the cis pyridine ligand in the A type structures (Scheme 2) [40,41].…”

Efficacy of a Binuclear Cyclopalladated Compound Therapy for Cutaneous Leishmaniasis in the Murine Model of Infection with Leishmania amazonensis and Its Inhibitory Effect on Topoisomerase 1B

“…In this context, several research groups have explored the potential therapeutic applications of cyclopalladated complexes (34, 41–46). Regarding kinetoplastid diseases, it has been shown that cyclopalladated complexes were efficacious in reducing the parasite load in an in vivo leishmanial cutaneous model (18) and exhibited trypanocidal potential for Chagas disease treatment (17).…”

Racemic 9,10-dimethoxy-3-methyl-6-phenyl-7,7a-dihydrobenzo[b]benzo[4,5]isothiazolo[2,3-d][1,4]diazepine 12,12-dioxide

“…For related structures, see: Zia-ul-Haq et al (2007); Boudina et al (2007); Doubia et al (2007); Sanudo et al (2009); Spencer et al (2009); Swamy et al (2008). For the psychotropic properties of aptazapine [systematic name: 2-methyl-1,3,4,14b-tetrahydro-2H,10H-pyrazino[1,2-a]pyrrolo[2,1-c][1,4]benzodiazepine] and bretazenil [systematic name: t-butyl-8-bromo-11,12,13,13a-tetrahydro-9-oxo-9H-imidazo(1,5-a)pyrrolo(2,1c)(1,4)benzodiazepine-1-carboxylate], see: Silvestri et al (1994); Landquist (1984); Insuasty et al (2008); Bennamane et al (2008); Schutz (1982).…”