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Type: Artigo
Title: Synthesis, DNA binding, and antiproliferative activity of novel acridine-thiosemicarbazone derivatives
Author: Vitalino de Almeida, Sinara Monica
Lafayette, Elizabeth Almeida
Bezerra Gomes da Silva, Lucia Patricia
da Cruz Amorim, Cezar Augusto
de Oliveira, Tiago Bento
Tasca Gois Ruiz, Ana Lucia
de Carvalho, Joao Ernesto
de Moura, Ricardo Olimpio
Carneiro Beltrao, Eduardo Isidoro
Alves de Lima, Maria do Carmo
de Carvalho Junior, Luiz Bezerra
Abstract: In 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 x 10(4) to 1.0 x 10(6) M-1 and quenching constants from -0.2 x 10(4) to 2.18 x 10(4) 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
Subject: Anticâncer
Atividade citotóxica
Country: Suiça
Editor: MDPI
Rights: Fechado
Identifier DOI: 10.3390/ijms160613023
Date Issue: 2015
Appears in Collections:CPQBA - Artigos e Outros Documentos

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