Tricarbonyl M(I) (M = Re, (99m)Tc) complexes bearing acridine fluorophores: synthesis, characterization, DNA interaction studies and nuclear targeting.
New pyrazolyl-diamine ligands with acridine derivatives at the 4-position of the pyrazolyl ring were synthesized and characterized (L1 and L2). Coordination towards the fac-[M(CO)(3)](+) (M = Re, (99m)Tc) led to complexes fac-[M(CO)(3)(kappa(3)-L)] (L = L1: M = Re1, Tc1; L = L2: M = Re2, Tc2). The interaction of the novel pyrazolyl-diamine ligands (L1 and L2) and rhenium(i) complexes (Re1 and Re2) with calf thymus DNA (CT-DNA) was investigated by a variety of techniques, namely UV-visible, fluorescence spectroscopy and circular and linear dichroism. Compounds L1 and Re1 have moderate affinity to CT-DNA and bind to DNA by intercalation, while L2 and Re2 have a poor affinity for CT-DNA. Moreover, LD measurements showed that L1 and Re1 act as perfect intercalators. By confocal fluorescence microscopy we found that L1 and Re1 internalize and localize in the nucleus of B16F1 murine melanoma cells. The congener Tc1 complex also targets the cell nucleus exhibiting a time-dependent cellular uptake and a fast and high nuclear internalization (67.2% of activity after 30 min). Plasmid DNA studies have shown that Tc1 converts supercoiled (sc) puc19 DNA to the open circular (oc) form.
Esteves
Teresa
T
Unidade de Ciências Químicas e Radiofarmacêuticas, ITN, Estrada Nacional 10, 2686-953 Sacavém, Portugal.
Xavier
Catarina
C
Gama
Sofia
S
Mendes
Filipa
F
Raposinho
Paula D
PD
Marques
Fernanda
F
Paulo
António
A
Pessoa
João Costa
JC
Rino
José
J
Viola
Giampietro
G
Santos
Isabel
I
D000166:Acridines / Q000737:chemistry*; D000818:Animals; D002417:Cattle; D045744:Cell Line, Tumor; D002467:Cell Nucleus / Q000378:metabolism*; D004247:DNA / Q000737:chemistry* / Q000187:drug effects / Q000378:metabolism; D004278:DNA, Superhelical / Q000737:chemistry / Q000187:drug effects; D008024:Ligands; D051379:Mice; D015394:Molecular Structure; D009942:Organometallic Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D010957:Plasmids / Q000737:chemistry / Q000187:drug effects; D012211:Rhenium / Q000737:chemistry*; D013237:Stereoisomerism; D013667:Technetium / Q000737:chemistry*
D000166:Acridines; D004278:DNA, Superhelical; D008024:Ligands; D009942:Organometallic Compounds; D012211:Rhenium; D013667:Technetium; D004247:DNA