Synthesis and biological studies of silver N-heterocyclic carbene complexes derived from 4,5-diarylimidazole.
A novel class of silver N-heterocyclic carbene complexes (5a-f) were synthesized in high yield by reacting silver(I) oxide with 4,5-diarylimidazolium halides (4a-f). The complexes were characterized using NMR and IR spectroscopy. The structure was confirmed on the example of bromo[1,3-diethyl-4,5-bis(4-fluorophenyl)imidazol-2-ylidene]silver(I) (5c) by crystal structure analysis. The X-ray structure indicated a three-dimensional coordination polymer with a repeating unit consisting of a C(carben)-Ag(2)-Br(2)-C(carben) cluster. Pharmacological investigations revealed that all silver complexes possessed growth inhibitory effects against breast cancer (MCF-7 and MDA-MB-231) as well as colon carcinoma (HT-29) cells. The most active compound 5c was slightly less active against MCF-7 cells, more active against MDA-MB-231 cells and comparable active as cisplatin against HT-29 cells. Further pharmacological investigations were performed with selected compounds on estrogen receptor (ER) binding, DNA intercalation, cyclooxygenase (COX) inhibition and antibacterial activity. The complexes were only marginally active at the DNA, ER and the COX enzymes, so these targets can be excluded to be involved in the mode of action. However, the growth of bacteria was significantly inhibited by 5c and 5f and opens a new application of this complex type.
Institute of Pharmacy, Freie Universität Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
Wukun
W
Liu
Kerstin
K
Bensdorf
Adelheid
A
Hagenbach
Ulrich
U
Abram
Ben
B
Niu
Aruljothi
A
Mariappan
Ronald
R
Gust
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001419:Bacteria / Q000187:drug effects; D001424:Bacterial Infections / Q000188:drug therapy; D001943:Breast Neoplasms / Q000188:drug therapy; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D005260:Female; D019073:HT29 Cells; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008697:Methane / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D012834:Silver / Q000737:chemistry* / Q000494:pharmacology*
D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D006571:Heterocyclic Compounds; D007093:Imidazoles; C030011:carbene; D012834:Silver; D008697:Methane