Anticancer activity of heteroleptic diimine complexes of dirhodium: a study of intercalating properties, hydrophobicity and in cellulo activity.
The series of complexes cis-[Rh(2)(mu-O(2)CCH(3))(2)(dppn)(L)](2+), where dppn = benzo[i]dipyrido[3,2-a:2',3'-c] phenazine, and L = bpy (2,2'-bipyridine) (1), phen (1,10-phenanthroline) (2), dpq (dipyrido[3,2-f:2',3'-h]quinoxaline) (3), dppz (dipyrido[3,2-a:2',3'-c]phenazine) (4), and dppn (5) were synthesized and their effect on the human cancer cells HeLa and COLO-316 was monitored. Complexes 1 and 2 interact with DNA through intercalation, whereas compounds 3-5 bind only electrostatically. It was found that the dirhodium complex 4 is the most effective compound at inhibiting cell viability of the human cancer cells HeLa and COLO-316. A general conclusion is that the hydrophobicity of the compounds correlates with their in cellulo activity in both cell lines. The ability of the compounds to reach nuclear DNA and form adducts was explored using the comet assay. The results indicate that compounds 1-5 either do not form adducts with DNA that are detrimental to the cell or that they are successfully repaired by the cellular machinery. The results of an annexin V assay indicate that compounds 1-4 trigger apoptosis, whereas compound 5 clearly does not. These findings are significant because they support the contention that dirhodium complexes can be tuned to direct their effect to cellular targets other than nuclear DNA.
Aguirre
J Dafhne
JD
Department of Chemistry, Texas A&M University, College Station, TX 77843, USA.
Angeles-Boza
Alfredo M
AM
Chouai
Abdellatif
A
Turro
Claudia
C
Pellois
Jean-Philippe
JP
Dunbar
Kim R
KR
D015082:2,2'-Dipyridyl / Q000737:chemistry; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000633:toxicity; D045744:Cell Line, Tumor; D020552:Comet Assay; D056831:Coordination Complexes / Q000737:chemistry* / Q000633:toxicity; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007097:Imines / Q000737:chemistry*; D007364:Intercalating Agents / Q000737:chemistry* / Q000633:toxicity; D010618:Phenanthrolines / Q000737:chemistry; D012238:Rhodium / Q000737:chemistry*
D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007097:Imines; D007364:Intercalating Agents; D010618:Phenanthrolines; D015082:2,2'-Dipyridyl; D004247:DNA; D012238:Rhodium; C025205:1,10-phenanthroline