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Thiazacridine and imidazacridine derivatives have shown promising results as tumors suppressors in some cancer cell lines. For a better understanding of the mechanism of action of these compounds, binding studies of 5-acridin-9-ylmethylidene-3-amino-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-thiazolidin-4-one, 5-acridin-9-ylmethylidene-2-thioxo-imidazolidin-4-one and 3-acridin-9-ylmethyl-thiazolidin-2,4-dione with calf thymus DNA (ctDNA) by electronic absorption and fluorescence spectroscopy and circular dichroism spectroscopy were performed. The binding constants ranged from OPEN ACCESSMolecules 2013, 18 15036 1.46 × 10 4 to 6.01 × 10 4 M −1 . UV-Vis, fluorescence and circular dichroism measurements indicated that the compounds interact effectively with ctDNA, both by intercalation or external binding. They demonstrated inhibitory activities to human topoisomerase I, except for 5-acridin-9-ylmethylidene-2-thioxo-1,3-thiazolidin-4-one. These results provide insight into the DNA binding mechanism of imidazacridines and thiazacridines.

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 × 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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RESUMO Este trabalho relata uma experiência de curricularização da extensão universitária no curso médico que teve como objetivos conduzir ações de extensão com vistas ao bem-estar de idosas de uma Instituição de Longa Permanência (ILP), bem como desenvolver habilidades do médico honesto, íntegro, cuidadoso, altruísta e empático consigo, com os “idosos” e com os pares envolvidos nas ações. O modelo usado para organização das atividades combinou métodos de aprendizagem de habilidades por meio da experiência, reflexão crítica sobre as experiências, ambiente de pequeno grupo para suporte e validação e programa longitudinal coeso para desenvolvimento total. As atividades foram vivenciadas em grupos de 12 integrantes, supervisionados por um professor com visitas semanais à ILP de agosto a dezembro de 2018. O modelo utilizado mostrou-se útil para o desenvolvimento de características humanísticas almejadas nos indivíduos em formação. O envolvimento em todas as etapas do processo e o comprometimento com o bem-estar da população selecionada indicam que a curricularização cumpriu seu papel de proporcionar aos estudantes o desenvolvimento de consciência cidadã em paralelo à formação técnica. A instituição de ensino superior deve oferecer continuamente ações para que os estudantes desenvolvam plenamente seu lado humano e preservem as características observadas no contato com a população idosa.

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