Synthesis of a 1,4-benzodiazepine containing palladacycle with in vitro anticancer and cathepsin B activity.
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.
Spencer
John
J
School of Science, University of Greenwich at Medway, Chatham Maritime, UK. j.spencer@gre.ac.uk
Rathnam
Rajendra P
RP
Motukuri
Mahesh
M
Kotha
Arun K
AK
Richardson
Simon C W
SC
Hazrati
Ali
A
Hartley
John A
JA
Male
Louise
L
Hursthouse
Michael B
MB
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D001569:Benzodiazepines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D002401:Cathepsin B / Q000037:antagonists & inhibitors* / Q000378:metabolism; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002522:Chlorocebus aethiops; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D020128:Inhibitory Concentration 50; D015464:Leukemia, Myelogenous, Chronic, BCR-ABL Positive / Q000188:drug therapy; D008099:Liver / Q000201:enzymology; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010165:Palladium / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D014709:Vero Cells
D000970:Antineoplastic Agents; D001569:Benzodiazepines; D010165:Palladium; D002401:Cathepsin B; C468549:Bz-423