Synthesis, Dna Binding, And Antiproliferative Activity Of Novel Acridine-thiosemicarbazone Derivatives.

dc.creatorde Almeida, Sinara Mônica Vitalino
dc.creatorLafayette, Elizabeth Almeida
dc.creatorda Silva, Lúcia Patrícia Bezerra Gomes
dc.creatorAmorim, Cézar Augusto da Cruz
dc.creatorde Oliveira, Tiago Bento
dc.creatorRuiz, Ana Lucia Tasca Gois
dc.creatorde Carvalho, João Ernesto
dc.creatorde Moura, Ricardo Olímpio
dc.creatorBeltrão, Eduardo Isidoro Carneiro
dc.creatorde Lima, Maria do Carmo Alves
dc.creatorde Carvalho Júnior, Luiz Bezerra
dc.date2015
dc.date2016-05-23T19:42:16Z
dc.date2016-05-23T19:42:16Z
dc.date.accessioned2018-03-29T01:29:36Z
dc.date.available2018-03-29T01:29:36Z
dc.identifierInternational Journal Of Molecular Sciences. v. 16, n. 6, p. 13023-13042, 2015.
dc.identifier1422-0067
dc.identifier10.3390/ijms160613023
dc.identifierhttp://www.ncbi.nlm.nih.gov/pubmed/26068233
dc.identifierhttp://repositorio.unicamp.br/jspui/handle/REPOSIP/235714
dc.identifier26068233
dc.identifier.urihttp://repositorioslatinoamericanos.uchile.cl/handle/2250/1303957
dc.descriptionIn 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.
dc.description16
dc.description13023-13042
dc.languageeng
dc.relationInternational Journal Of Molecular Sciences
dc.relationInt J Mol Sci
dc.rightsaberto
dc.sourcePubMed
dc.subjectDna Binding
dc.subjectAcridine
dc.subjectAntiproliferative
dc.subjectThiosemicarbazone
dc.titleSynthesis, Dna Binding, And Antiproliferative Activity Of Novel Acridine-thiosemicarbazone Derivatives.
dc.typeArtículos de revistas


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