In vitro evaluation of triazenes: DNA cleavage, antibacterial activity and cytotoxicity against acute myeloid leukemia cells

Abstract

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...

Synthesis, characterization and biological activity of a gold(I) triazenide complex against chronic myeloid leukemia cells and biofilm producing microorganisms

“…Several studies using TZC compounds have shown that these compounds have broad antimicrobial activity (Hörner et al 2008;Domingues et al, 2010;Ombaka et al, 2012;Paraginski et al, 2014;Tizotti et al, 2016). Studies suggest that the antibacterial action of TZCs is due to the chelating activity of metal ions that are constituents of the bacteria cell wall, hindering their synthesis and leading to cell death (Hörner et al 2008;Ombaka et al, 2012).…”

“…Barreiro et al (2012) reported that this metal acts inhibiting bacterial proliferation by blocking cell cytokinesis (Barreiro et al, 2012). Domingues et al (2010), obtained MIC values>128 mg/mL using TZCs not complexed with metal compounds against an S. epidermidis clinical isolate, as well as S. epidermidis ATCC 12128 strain (Domingues et al, 2010). In addition, another study using 15 TZC compounds not associated with metal showed MIC values=64 mg/mL for hospital isolates of S. epidermidis and S. saprophyticus (Horner et al, 2008).…”

“…Triazene compounds (TZCs) are characterized by the diazoamine group (N = N-N) (Moore, Robinson, 1986), which accounts for their biological properties (Marchesi et al, 2007). They have a broad pharmacological versatility: antibacterial (Horner et al, 2008;Domingues et al, 2010;Ombaka, Muguna, Gichumbi, 2012;Tizotti et al, 2016), antifungal (Ombaka, Muguna, Gichumbi, 2012), antileukemic (Matheson et al, 2004;Domingues et al, 2010;Bonmassar et al, 2013;Tizotti et al, 2016), and synthetic nuclease (Domingues et al, 2010). Dacarbazina® and Temozolomida® are examples of TZC compounds widely used in the clinical treatment of various malignancies (Bonmassar et al, 2013).…”

Synthesis and Antibacterial Evaluation of 2-Ethyl-1-(4-substituted)phenyl- 1H-imidazole Derivatives as Open-Chain Analogues of 7-Alkoxyl-4,5-dihydroimidazo[1,2-a]quinolines

“…These bacteria easily cause severe infection illness or food poisoning, and at the same time, they are widely applied to the antimicrobial activity screening experiments. [14][15][16][17] Analysis of the data in Table 2 showed that the compound 5l exhibited inhibitory activity against P. aeruginosa, K. pneumoniae, P. vulgaris, and S. typhimurium in the entire dose range of 8-256 nmol mL -1 , but was found to be inactive against P. multocida at even the highest concentration of 256 nmol mL -1 . The MIC of 5l against P. aeruginosa was found to be 8 nmol mL -1 , which was similar to that of the control ciprofloxacin, and lower than that of amoxicillin.…”

Vibrational studies, NMR analysis, modeling of electronic and thermodynamical parameters of 1,3-bis(4-benzamido)triazene

“…The geometrical parameters including bond length, bond angle and dihedral angles were presented in Table 1. Since the crystal structure of BBT is not available, the optimized structure was compared with other similar optimized compounds [26,27]. The molecule contains two CO-NH 2 groups and triazeno moiety with two benzene rings.…”