Details

Autor(en) / Beteiligte

• de Almeida, Sinara Mônica Vitalino
• Lafayette, Elizabeth Almeida
• da Silva, Lúcia Patrícia Bezerra Gomes
• Amorim, Cézar Augusto da Cruz
• de Oliveira, Tiago Bento
• Ruiz, Ana Lucia Tasca Gois
• de Carvalho, João Ernesto
• de Moura, Ricardo Olímpio
• Beltrão, Eduardo Isidoro Carneiro
• de Lima, Maria do Carmo Alves
• de Carvalho Júnior, Luiz Bezerra

Titel

Synthesis, DNA Binding, and Antiproliferative Activity of Novel Acridine-Thiosemicarbazone Derivatives

Ist Teil von

• International journal of molecular sciences, 2015-06, Vol.16 (6), p.13023-13042

Ort / Verlag

Switzerland: MDPI AG

Erscheinungsjahr

2015

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 × 10(4) to 1.0 × 10(6) M(-1) and quenching constants from -0.2 × 10(4) to 2.18 × 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.