Produção Nacional
Revisado por pares
Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives
2015; Multidisciplinary Digital Publishing Institute; Volume: 16; Issue: 6 Linguagem: Inglês
10.3390/ijms160613023
ISSN1661-6596
AutoresSinara De Almeida, Elizabeth Almeida Lafayette, Lúcia Da Silva, Cézar Augusto da Cruz Amorim, Tiago E. de Oliveira, Ana Lúcia Tasca Góis Ruiz, João de Carvalho, Ricardo Olímpio de Moura, Eduardo Isidoro Carneiro Beltrão, Maria C. Pedroso de Lima, Luiz Júnior,
Tópico(s)Synthesis and biological activity
ResumoIn this work, the acridine nucleus was used as a lead-compound for structural modification by adding different substituted thiosemicarbazide moieties. Eight new (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide derivatives (3a–h) were synthesized, their antiproliferative activities were evaluated, and DNA binding properties were performed with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopies. Both hyperchromic and hypochromic effects, as well as red or blue shifts were demonstrated by addition of ctDNA to the derivatives. The calculated binding constants ranged from 1.74 × 104 to 1.0 × 106 M−1 and quenching constants from −0.2 × 104 to 2.18 × 104 M−1 indicating high affinity to ctDNA base pairs. The most efficient compound in binding to ctDNA in vitro was (Z)-2-(acridin-9-ylmethylene)-N- (4-chlorophenyl) hydrazinecarbothioamide (3f), while the most active compound in antiproliferative assay was (Z)-2-(acridin-9-ylmethylene)-N-phenylhydrazinecarbothioamide (3a). There was no correlation between DNA-binding and in vitro antiproliferative activity, but the results suggest that DNA binding can be involved in the biological activity mechanism. This study may guide the choice of the size and shape of the intercalating part of the ligand and the strategic selection of substituents that increase DNA-binding or antiproliferative properties.
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