Author(s): Esteves, Teresa ; Xavier, Catarina ; Gama, Sofia ; Mendes, Filipa ; Raposinho, Paula D. ; Marques, Fernanda ; Paulo, António ; Pessoa, João Costa ; Rino, José ; Viola, Giampietro ; Santos, Isabel
Date: 2010
Persistent ID: http://hdl.handle.net/10451/7119
Origin: Repositório da Universidade de Lisboa
Subject(s): Acridine; Fluorescence spectroscopy; Radiopharmaceuticals; Cell nucleus; DNA
© The Royal Society of Chemistry 2010
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, 99mTc) led to complexes fac-[M(CO)3(κ3-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.
Teresa Esteves and Sofia Gama thank the FCT for a doctoral and postdoctoral research grants (SFRH/BD/29154/2006 and SFRH/BPD/29564/2006, respectively). COST Action D39 is also acknowledge. The QITMS instrument was acquired with the support of the Programa Nacional de Reequipamento Científico (Contract>REDE/1503/REM/2005-ITN) of Fundação para a Ciência e a Tecnologia and is part of RNEM - Rede Nacional de Espectrometria de Massa.
