Polymer-cobalt(III) complexes: structural analysis of metal chelates on DNA interaction and comparative cytotoxic activity.
A new series of pendant-type polymer-cobalt(III) complexes, [Co(LL)2(BPEI)Cl](2+), (where BPEI = branched polyethyleneimine, LL = dipyrido[3,2-a:2',3'-c](6,7,8,9-tetrahydro)phenazine (dpqc), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) and imidazo[4,5-f]1,10-phenanthroline (ip)) each with three different degrees of coordination have been synthesized and characterized. Studies to know the mode and strength of interaction between these polymer-metal complexes and calf thymus DNA have been performed by UV-Visible absorption and emission techniques. Among these series, each polymer metal complex having higher binding strength with DNA has been selected to test against human cancer/normal cell lines. On the basis of these spectral studies, it is proposed that our polymer-metal complexes bind with DNA mainly through intercalation along with some electrostatic binding. The order of binding strength for the complexes with ligand, dpqc > dpq > ip. The analysis of the results suggests that polymer-cobalt(III) complexes with higher degree of coordination effectively binds with DNA due to the presence of large number of positively charged cobalt(III) chelates in the polymer chain which cooperatively act to increase the overall binding strength. These polymer-cobalt(III) complexes with hydrophobic ligands around the cobalt(III) metal centre favour the base stacking interactions via intercalation. All the complexes show very good anticancer activities and increasing of binding strength results in higher inhibition value. The polymer-cobalt(III) complex with dpqc ligand possess two fold increased anticancer activity when compared to complexes with other ligands against MCF-7 cells. Besides, the complexes were insensitive towards the growth of normal cells (HEK-293) at the IC50 concentration.
a School of Chemistry, Bharathidasan University , Tiruchirappalli , Tamil Nadu , 620 024 , India .
Selvan
S
Nehru
Sankaralingam
S
Arunachalam
Renganathan
R
Arun
Kumpati
K
Premkumar
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002417:Cattle; D002470:Cell Survival / Q000187:drug effects; D002614:Chelating Agents / Q000737:chemistry* / Q000494:pharmacology; D003035:Cobalt; D056831:Coordination Complexes / Q000737:chemistry* / Q000494:pharmacology; D004247:DNA / Q000378:metabolism*; D053938:DNA Fragmentation / Q000187:drug effects; D057809:HEK293 Cells; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D007364:Intercalating Agents / Q000737:chemistry* / Q000494:pharmacology; D061986:MCF-7 Cells; D010618:Phenanthrolines / Q000737:chemistry; D011094:Polyethyleneimine / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship
D002614:Chelating Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D010618:Phenanthrolines; D003035:Cobalt; D011094:Polyethyleneimine; D004247:DNA; C427203:calf thymus DNA
DNA binding; branched polyethyleneimine; cytotoxicity; intercalation and electrostatic binding; polymer–cobalt(III) complexes