triazeno (3) foram avaliadas quanto à capacidade de clivagem do DNA plasmidial pUC18 e pBSKII, atividade antibacteriana e citotoxicidade in vitro frente a células de leucemia mielóide aguda e leucócitos normais utilizando o bioensaio da redução do sal brometo de 3-(4,5-dimetiltiazol-2-il)-2,5-difeniltetrazólio (MTT). Os triazenos analisados demonstraram capacidade de clivagem dos dois tipos de DNA plasmidial: triazeno 1 em pH 8,0 e 50 °C; triazeno 2 em pH 6,5 a 37 e 50 °C; triazeno 3 em pH 6,5 e 37 °C. Os compostos apresentaram atividade citotóxica frente a células leucêmicas. O composto 1 mostrou alta atividade frente a B. cereus (CIM = 32 mg mL -1 ). A associação molecular através de ligações de hidrogênio no estado sólido do composto 3 com base na análise estrutural por difratometria de raios X em monocristal, bem como os resultados das análises espectroscópicas nas regiões do IV e UV-Vis dos compostos 1, 2 e 3 são discutidos no presente trabalho.The asymmetric diazoamines 1-(2-chlorophenyl)-3-(4-carboxyphenyl)triazene (1), 1-(2-fluorophenyl)-3-(4-carboxyphenyl)triazene (2) and 1-(2-fluorophenyl)-3-(4-amidophenyl) triazene (3) were evaluated for their ability to cleave pUC18 and pBSKII plasmid DNA, antibacterial activity and in vitro cytotoxicity against acute myeloid leukemia cells and normal leukocytes using the bioassay of reduction of 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT). The triazenes showed ability to cleave the two types of plasmid DNA: triazene 1 at pH 8.0 and 50 °C; triazene 2 at pH 6.5 and 37 and 50 °C; triazene 3 at pH 6.5 and 37 °C. The compounds presented cytotoxic activity against myeloid leukemia cells. Compound 1 showed high activity against B. cereus (MIC = 32 mg mL -1 ). The observation of intermolecular hydrogen bonding in the solid state of compound 3, based on the structural analysis by X-ray crystallography, as well as the results of IR and UV-Vis spectroscopic analyses of compounds 1, 2 and 3 are discussed in the present work.Keywords: triazenes, DNA cleavage, antibacterial activity, cytotoxicity
IntroductionTriazenes or diazoamines constitute a class of compounds containing three consecutive nitrogen atoms in an acyclic arrangement. 1 Diazoamino compounds can be obtained by diverse synthetic ways, the classical method including the coupling reaction of a diazonium salt, [R-N≡N] + X -, with an amine (R'-NH 2 ) in acidic medium. This is followed by formation of the respective diazoamino compound R-N=N-N(H)-R' (R = R' for Domingues et al. 2227 Vol. 21, No. 12, 2010 symmetric triazenes; R ≠ R' for asymmetric compounds) by stepwise neutralization of the reaction system. They have diverse applications as DNA alkylating agents in tumor therapy, protecting groups in natural product synthesis and combinatorial chemistry, as well as precursors incorporated into polymer and oligomer synthesis. [2][3][4][5][6][7][8] Hydrolysis of DNA or RNA catalyzed by relevant enzymes is an important subject in biotechnology, medicine and drug development. 9,10 Synthetic nuclease...