Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA

TY - JOUR

T1 - Syntheses of polypyridyl metal complexes and studies of their interaction with quadruplex DNA

AU - Stafford, Verity S.

AU - Suntharalingam, Kogularamanan

AU - Shivalingam, Arun

AU - White, Andrew J P

AU - Mann, David J.

AU - Vilar, Ramon

PY - 2015/2/28

Y1 - 2015/2/28

N2 - A series of mono- and bi-metallic metal complexes (with CuII, PtII and ZnII) with substituted polypyridyl ligands have been prepared and their binding affinities towards quadruplex (c-Myc and human telomeric) and duplex DNA (ds26 and calf thymus) determined using fluorescent indicator displacement (FID) assays and UV/vis spectroscopic titrations. These studies have shown that the number of aromatic rings and number/position of cyclic amine substituents on the ligands, play an important role in defining the DNA binding abilities of the resulting metal complexes. We also show that bi-metallic complexes prepared using a novel terpyridine-cyclen ligand have higher affinity towards G-quadruplex DNA as compared to their mono-metallic counterparts. Cytotoxicity assays were carried out for all the new complexes against an osteosarcoma cancer cell line (U2OS) as well as a normal fibroblast cell line (GM05757). Several of these compounds displayed cytotoxicity similar to that of cisplatin. This journal is

AB - A series of mono- and bi-metallic metal complexes (with CuII, PtII and ZnII) with substituted polypyridyl ligands have been prepared and their binding affinities towards quadruplex (c-Myc and human telomeric) and duplex DNA (ds26 and calf thymus) determined using fluorescent indicator displacement (FID) assays and UV/vis spectroscopic titrations. These studies have shown that the number of aromatic rings and number/position of cyclic amine substituents on the ligands, play an important role in defining the DNA binding abilities of the resulting metal complexes. We also show that bi-metallic complexes prepared using a novel terpyridine-cyclen ligand have higher affinity towards G-quadruplex DNA as compared to their mono-metallic counterparts. Cytotoxicity assays were carried out for all the new complexes against an osteosarcoma cancer cell line (U2OS) as well as a normal fibroblast cell line (GM05757). Several of these compounds displayed cytotoxicity similar to that of cisplatin. This journal is

UR - http://www.scopus.com/inward/record.url?scp=84922775361&partnerID=8YFLogxK

U2 - 10.1039/c4dt02910k

DO - 10.1039/c4dt02910k

M3 - Article

AN - SCOPUS:84922775361

SN - 1477-9226

VL - 44

SP - 3686

EP - 3700

JO - Dalton transactions (Cambridge, England : 2003)

JF - Dalton transactions (Cambridge, England : 2003)

IS - 8

ER -