Bacterial resistance to antibacterial agents is currently a major concern. We report the synthesis, in vitro antibacterial activity and toxicity toward Artemia salina of six diaryltriazene compounds bearing different substituent groups. Minimal Inhibitory Concentration (MIC) and Minimal Bactericidal Concentration (MBC) values against standard strains (ATCC) and clinical isolates (including ESBL, MBL and AmpC strains) were good to very good, in the range 8 to 128 mg mL-1. Results suggest that hydroxyl, 4-carboxyl and 4-phenyldiazenil groups attached to the diaryltriazenes provide enhanced activity. Toxicity results showed very low LC50 values for three compounds (10-fold lower than DTIC).

As diazoaminas assimétricas 1-(2-clorofenil)-3-(4-carboxifenil)triazeno (1), 1-(2-fluorofenil)-3-(4-carboxifenil)triazeno (2) e 1-(2-fluorofenil)-3-(4-amidofenil)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 ºC; triazeno 2 em pH 6,5 a 37 e 50 ºC; triazeno 3 em pH 6,5 e 37 ºC. 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 ºC; triazene 2 at pH 6.5 and 37 and 50 ºC; triazene 3 at pH 6.5 and 37 ºC. 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.

Quinze compostos triazenos foram estudados quanto à atividade antibacteriana pela metodologia de microdiluição em caldo. A Concentração Inibitória Mínima (CIM) e a Concentração Bactericida Mínima (CBM) foram pesquisadas frente a três bactérias padrão (E. coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853) e frente a cepas hospitalares (Acinetobacter baumannii, Acinetobacter lwoffii, Ralstonia pickettii, Bordetella bronchiseptica, Micrococcus sp., Enterococcus sp., Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae, Bacillus cereus, Corynebacterium sp., Rhodococcus sp., Salmonella sp., Serratia marcescens, Morganella morganii, Enterobacter cloacae, Shigella flexneri, Shigella sonnei, Shigella sp., Klebsiella pneumoniae, ESBL Klebsiella oxytoca 14, ESBL Klebsiella pneumoniae 23, ESBL Klebsiella pneumoniae 24, ESBL Klebsiella pneumoniae 25, ESBL Escherichia coli 26, ESBL Klebsiella pneumoniae 27, ESBL Klebsiella pneumoniae 31, ESBL Escherichia coli 32, ESBL Klebsiella pneumoniae 37 e ESBL Escherichia coli 38). A maior atividade foi evidenciada para o composto 1-metil-3-(p-carboxifenil)triazeno 1-óxido (2) contra Streptococcus agalactiae (CIM =16 µg/mL e CBM = 32 µg/mL). Os compostos 1-fenil-3-(4-nitrofenil)triazeno-1-óxido (9), 1-(4-nitrofenil)-3-(4-carboxifenil)triazeno (10) e 1-(4-acetilaminofenil)-3-(4-carboxifenil)triazeno (11) apresentaram CIMs de 32 a 64 µg/mL frente a S. edipermidis, S. saprophyticus, Corynebacterium sp. e E. cloacae. Os compostos 1-metil-3-feniltriazeno-1-óxido (1) , bis-1,3-(4-acetiloxima)triazeno (3), bis-1,3 (4-acetilfenil)triazeno (4), 1-(2-fluorfenil)-3-(4-acetilfenil)triazeno (5), 1,3-(3-hidroxi-difeniltriazenido)(piridil)(bis-oxo-vanádio) (12), 1-(3-nitrofenil)-3-feniltriazeno (14), 1-(4-nitrofenil)-3-benziltriazeno (15) apresentaram CIM = 128 µg/mL frente a S. aureus ATCC 25923, P. aeruginosa ATCC 27853, A. lwoffii, Micrococcus sp., S. epidermidis, S. saprophyticus, Corynebacterirum sp., E. cloacae, S. flenneri e S. sonnei. Os compostos 1-fenil-3-(4-acetilfenil)triazeno (6), 1,3-bis-(4-etoxicarbonilfenil) triazeno (7) e 3-(4-carboxilatofenil)-1-metiltriazeno 1-óxido de potássio tetraidratado (13) apresentaram CIMs iguais ou maiores que 128 µg/mL. Estes resultados demonstraram a potencial atividade biológica destes compostos contra bactérias Gram-positivas e Gram-negativas.

Fifteen triazenes compounds were studied concerning their antibacterial activity by broth microdilution method. Minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) was determined with E. coli ATCC 25922, Staphylococcus aureus ATCC 25923, Pseudomonas aeruginosa ATCC 27853, Acinetobacter baumannii, Acinetobacter lwoffii, Ralstonia pickettii, Bordetella bronchiseptica, Micrococcus sp., Enterococcus sp., Staphylococcus epidermidis, Staphylococcus saprophyticus, Streptococcus agalactiae, Bacillus cereus, Corynebacterium sp., Rhodococcus sp., Salmonella sp., Serratia marcescens, Morganella morganii, Enterobacter cloacae, Shigella flexneri, Shigella sonnei, Shigella sp., Klebsiella pneumoniae, ESBL Klebsiella oxytoca 14, ESBL Klebsiella pneumoniae 23, ESBL Klebsiella pneumoniae 24, ESBL Klebsiella pneumoniae 25, ESBL Escherichia coli 26, ESBL Klebsiella pneumoniae 27, ESBL Klebsiella pneumoniae 31, ESBL Escherichia coli 32, ESBL Klebsiella pneumoniae 37 e ESBL Escherichia coli 38. The highest effect was evidenced by the compound 1-methyl-3-(p-carboxyphenyl)triazene 1-oxide (2) against Streptococcus agalactiae (MIC = 16 µg/mL and MBC = 32 µg/mL). The compounds 1-phenyl-3-(4-nitrophenyl)triazene-1-oxide (9), 1-(4-nitrophenyl)-3-(4-carboxyphenyl)triazene (10) e 1-(4-acethyl amine phenyl)-3-(4-carboxyphenyl)triazene (11) presented MIC between 32 and 64 µg/mL against S. edipermidis, S. saprophyticus, Rhodococcus sp. and E. cloacae. The compounds 1-methyl-3-phenyltriazene-1-oxide (1) , bis-1,3-(4-acethyl oxime)triazene (3), bis-1,3 (4-acethyl phenyl)triazene (4), 1-(2-fluorophenyl)-3-(4-acethylphenyl)triazene (5), 1,3-(3-hydroxy-diphenyltriazenide)(piridil)(bis-oxo-vanadium) (12), 1-(3-nitrophenyl)-3-phenyltriazene (14), 1-(4-nitrophenyl)-3-benzyltriazene (15) presented MIC of the 128 µg/mL against S. aureus ATCC 25923, P. aeruginosa ATCC 27853, A. lwoffii, Micrococcus sp., S. epidermidis, S. saprophyticus, Corynebacterirum sp., E. cloacae, S. flenneri e S. sonnei. The compounds 1-phenyl-3-(4-acethylphenyl)triazene (6), 1,3-bis-(4-ethoxycarbonylphenyl) triazene (7), and 3-(4-carboxylatephenyl)-1-methyltriazene 1-oxide of potassium tetrahydrate (13) presented MICs equals or highest than 128 µg/mL. The results have demonstrated the potential biological activity of these compounds against Gram-positive and Gram-negative bacteria.