SÃntese e avaliaÃÃo da atividade biolÃgica de novos derivados acridino-tiazolidÃnicos e acridino-imidazolidÃnicos / SÃntese e avaliaÃÃo da atividade biolÃgica de novos derivados acridino-tiazolidÃnicos e acridino-imidazolidÃnicos

AUTOR(ES)
DATA DE PUBLICAÇÃO

2003

RESUMO

The acridines compounds present an ample variety of biological effect that can be attributed, in its great majority, its ability to bind the DNA, intercalating themselves it between the pairs of basis and blocking the action of topoisomerases I and II. In literature, compounds possessing the acridine ring are distinguished for presenting activities antimalarial, antibacterial, antileishmanial, antitripanossomal and anticancer. In this work, new derivatives acridine-thiazolines and acridineimidazolidines had been synthecized and evaluated for the antitumoral activity in vivo. These derivatives had been obtained by means synthetic in some stages: initially, thiazolidine-2,4-dione reacted with benzyl chlorides or bromides, leading substituted 3-benzyl-tiazolidine-2,4-dione. Parallel, the 9-methyl-acridine was obtained through the reaction of the acetic acid glacial with diphenylamine. The 9- methyl-acridine was oxidated to 9-acridinaldehyde by the piridinium chlorochromate, under inert atmosphere. This aldehyde, reacted with the ethyl-cyanacetate through Knoevenagel condensation leading the ethyl-2-cyan-acridine-9-yl-acrilate. The last stage consists of the reaction of addition type Michael between 3-benzyl-thiazolidine- 2,4-dione and ethyl-2-cyan-acridine-9-yl-acrilate. In the synthesis of acridineimidazolidine derivatives, the initial product is imidazolidine-2,4-dione that reacts with benzyl chlorides or bromides leading 3-benzyl-imidazolidine-2,4-dione. The thionation with tetraphosphorous decasulfide leads to the 4-thio-imidazolidin-2-one compounds. The condensation with ethyl-2-cyan-acridine-9-yl-acrilate getting the acridineimidazolidines products. The chemical structure of these compounds had been determined by infrared spectra, hydrogen nuclear magnetic resonance spectra and mass spectra.The acridine compounds had been submitted the tests for evaluation of antitumoral activity in vivo, using sarcoma 180. The results indicate an important inhibition of the growth of the tumorale cells, where the derivatives with nitro and bromine in position 4 of phenyl ring are most active presenting a percentage of inhibition of 71,48% and 72,24% respectively, in the dose of 50mg/kg of weight.

ASSUNTO(S)

ciencias biologicas dna acridines compounds dna compostos acridinos

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