PMID- 23964823
OWN - NLM
STAT- MEDLINE
DCOM- 20131126
LR  - 20220408
IS  - 1520-4804 (Electronic)
IS  - 0022-2623 (Linking)
VI  - 56
IP  - 18
DP  - 2013 Sep 26
TI  - Novel mixed-ligand copper(I) complexes: role of diimine ligands on cytotoxicity 
      and genotoxicity.
PG  - 7416-30
LID - 10.1021/jm400965m [doi]
AB  - Novel tetrahedral copper(I) mixed-ligand complexes of the type 
      [Cu(X)(N( intersection)N)(PCN)], 3-10, where X = Cl or Br, N( intersection)N = 2,2'-bipyridine (bipy), 
      1,10-phenanthroline (phen), 5,6-dimethyl-1,10-phenanthroline (dmp), and 
      dipyrido-[3,2-d:2',3'-f]-quinoxaline (dpq), and PCN = 
      tris-(2-cyanoethyl)phosphine, have been synthetized and characterized by NMR, 
      ESI-MS, and X-ray diffraction on two representative examples, 
      [CuCl(phen)(PCN)].DMF (5.DMF) and [CuBr(dpq)(PCN)].2DMF (10.2DMF). Cu(I) 
      complexes were evaluated for their in vitro antitumor properties against a panel 
      of human cancer cell lines, including cisplatin- and multidrug-resistant 
      sublines. The most effective complex, [CuCl(dpq)(PCN)] (9), exhibited nanomolar 
      cytotoxicity toward both sensitive and resistant cancer cells, but it 
      significantly inhibited the growth of cultured normal cells. In vitro DNA assays 
      and single cell gel electrophoresis revealed that 9 induced DNA fragmentation 
      resulting in cell apoptosis. In parallel, fluorescence in situ hybridization 
      (FISH) micronucleus assay attested high levels of genotoxicity following 
      treatment of peripheral blood lymphocytes with complex 9, suggesting that the 
      potential risk posed by diimine metal complexes should be carefully reconsidered.
FAU - Gandin, Valentina
AU  - Gandin V
AD  - Dipartimento di Scienze del Farmaco, Universita di Padova , via Marzolo 5, 35131 
      Padova, Italy.
FAU - Porchia, Marina
AU  - Porchia M
FAU - Tisato, Francesco
AU  - Tisato F
FAU - Zanella, Alessandro
AU  - Zanella A
FAU - Severin, Emilia
AU  - Severin E
FAU - Dolmella, Alessandro
AU  - Dolmella A
FAU - Marzano, Cristina
AU  - Marzano C
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130910
PL  - United States
TA  - J Med Chem
JT  - Journal of medicinal chemistry
JID - 9716531
RN  - 0 (Aneugens)
RN  - 0 (Antineoplastic Agents)
RN  - 0 (Imines)
RN  - 0 (Ligands)
RN  - 0 (Organometallic Compounds)
RN  - 789U1901C5 (Copper)
RN  - 9007-49-2 (DNA)
SB  - IM
MH  - Aneugens/adverse effects/chemistry/metabolism/pharmacology
MH  - Antineoplastic Agents/adverse effects/chemistry/metabolism/pharmacology
MH  - Biological Transport
MH  - Cell Cycle/drug effects
MH  - Cell Line, Tumor
MH  - Copper/*chemistry
MH  - DNA/genetics/metabolism
MH  - DNA Fragmentation/drug effects
MH  - Humans
MH  - Imines/*chemistry
MH  - Ligands
MH  - Micronucleus Tests
MH  - Models, Molecular
MH  - Molecular Conformation
MH  - Organometallic Compounds/*adverse effects/chemistry/metabolism/*pharmacology
MH  - Structure-Activity Relationship
EDAT- 2013/08/24 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/08/23 06:00
PHST- 2013/08/23 06:00 [entrez]
PHST- 2013/08/24 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - 10.1021/jm400965m [doi]
PST - ppublish
SO  - J Med Chem. 2013 Sep 26;56(18):7416-30. doi: 10.1021/jm400965m. Epub 2013 Sep 10.