Abstract INTRODUCTION: Coagulase-negative staphylococci (CoNS) are a frequent cause of bacteremia, especially in neonates. The major virulence determinant in CoNS is the ability to produce biofilms, which is conferred by the icaADBC genes. This study aimed to assess different methods for the detection of biofilm formation in 176 CoNS isolates from blood cultures of newborns. METHODS: The presence of the icaACD genes was assessed by polymerase chain reaction (PCR), and biofilm formation was assessed on congo red agar (CRA), by the tube method (TM), and on tissue culture plates (TCP). RESULTS: Of the 176 CoNS isolates, 30.1% expressed icaACD and 11.4% expressed icaAD. The CRA assay and TM showed that 42% and 38.6% of the isolates were biofilm producing, respectively. On TCP, 40.9% of the isolates produced biofilms; 21% were weakly adherent and 19.9% were strongly adherent. When compared to the gold standard technique (PCR), the CRAassay showed 79% sensitivity and 84% specificity (kappa = 0.64), TM showed 78% sensitivity and 89% specificity (kappa = 0.68), and TCP showed 99% sensitivity and 100% specificity (kappa = 0.99). CONCLUSIONS: In this study, ~42% of CoNS isolates produced biofilms, and the presence of icaACD was associated with a greater capacity to form biofilms. Compared to the other phenotypic methodologies, TCP is an ideal procedure for routine laboratory use.

Abstract The treatment of infections caused by resistant microorganisms represents a big challenge in healthcare due to limited treatment options. For this reason, the discovery of new active substances which are able to perform innovative and selective actions is of great impact nowadays. Statins and triazenes (TZC) have consolidated as a promising class of compounds, characterized by the expressive biological activity, especially antimicrobial activities. The aim of this study was to assess the in vitro synergistic antibacterial effect of the association of statins and a new TZC complex {[1-(4-bromophenyl)-3-phenyltriazene N 3-oxide-κ 2 N 1,O 4](dimethylbenzylamine-κ 2 C 1,N 4)palladium(II)} (Pd(DMBA)LBr) against American Type Culture Collection (ATCC) strains and clinical isolates. The complex and the statins showed bacterial activity of all tested strains and clinical isolates, evidencing that TZC complexion with metals can be promising. Simvastatin showed synergy when associated to the complex (FICI≤0.5), being the minimum inhibitory concentration (MIC) of 16 µg mL-1 found in 6 samples. Thus, it is possible to infer that the association between Pd(DMBA)LBr and simvastatin consists of an alternative to increase the pontential of these compounds, since statins have low toxicity.

Abstract INTRODUCTION: In this study, we used phenotypic methods to screen carbapenem-resistant Enterobacteriaceae (CREs) and evaluated their antimicrobial sensitivity profile. METHODS: One hundred and seventy-eight CREs were isolated at a university hospital in south Brazil in a one-year period. Samples were assessed using disk diffusion tests with inhibitors of β-lactamases such as phenylboronic acid (AFB), cloxacillin (CLOXA), and ethylenediaminetetraacetic acid (EDTA). Strains with differences in zone diameters ≥ 5mm for disks supplemented or not were considered producers of carbapenemases. RESULTS: Klebsiella pneumoniae was the most prevalent CRE, which appeared in 80.3% cases (n = 143). Among clinical materials, the rectal swab was responsible for 43.4% of the isolations (n = 62), followed by urine (18.9%; n = 27). Among the CREs identified in this study, the growth of 56.7% (n = 101) isolates, which were putative producers of Klebsiella pneumoniae carbapenemase (KPC), were inhibited by AFB, whereas 7.3% (n = 13) isolates were inhibited by both AFB and CLOXA and were considered as putative producers of plasmid-mediated AmpC; approximately 3.4% (n = 6) were inhibited by EDTA, which possibly produced metallo-β-lactamase. Lastly, 32.6% (n = 58) cases showed negative results for AFB, CLOXA, and EDTA sensitivity, and represented another class of β-lactamases and/or mechanism of resistance. CONCLUSIONS: Phenotypic screening of CREs is important for clinical laboratories that monitor outbreaks of resistant microbes. Phenotypic tests that use carbapenemase inhibitors and enhancers such as AFB, CLOXA, and EDTA are necessary since they are good screening methods for the detection of carbapenemases.

ABSTRACT The enhancement of anti-leukemia therapy and the treatment of infections caused by multidrug-resistant pathogens are major challenges in healthcare. Although a large arsenal of drugs is available, many of these become ineffective, and as a result, the discovery of new active substances occurs. Notably, triazenes (TZCs) have been consolidated as a promising class of compounds, characterized by significant biological activity, especially antiproliferative and antimicrobial properties. The aim of this study is the synthesis and characterization of a new triazenide complex of gold (I), as well as the in vitro assessment of its antiproliferative activity against the K562 cell line (Chronic Myeloid Leukemia), and antibacterial activity against bacterial isolates of biofilm-producing coagulase-negative staphylococci. The combination of TZC with gold metal tends to have a synergistic effect against all biofilm-producing isolates, with Minimum Inhibitory Concentration values (MIC) between 32 and 64 µg mL-1. It has also shown activity against K562 cell line, getting an IC50=4.96 µM. Imatinib mesylate (Glivec) was used as reference, with IC50=3.86 µM. To the best of our knowledge, this study represents the first report of the activity of a TZC complexed with gold ion in the oxidation state (I) against microorganisms that produce biofilm and K562 cells.

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.

The reaction of 4-(phenyl)thiosemicarbazide with isatin yielded a new ligand, isatin-3-(N4-benzylthiosemicarbazone). Isatin-3-(N4-benzylthiosemicarbazone) deprotonated in ethanol/KOH reacts with an ethanolic solution of Hg(NO3)2 to give a mercury complex. The compounds were characterized by IR and X-ray single crystal structure determination. The X-ray studies revealed that the complex possesses a tetrahedral geometry with two deprotonated thiosemicarbazone ligands coordenated. The ligand and its mercury complex crystallize in the monoclinic (P2(1)/c) and triclinic (P-1) crystal system, respectively.

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.

1,3-bis(4-etoxicarbonilfenil)triazeno desprotonado reage com Hg(CH3COO)2 em tetraidrofurano para formar cristais amarelos de {[HgII(RC6H4NNNC6H4R)2Py]2}n [R = EtOC(O)]. Os téctons [HgII(RC6H4NNNC6H4R)2Py] encontram-se ligados aos pares como dímeros centro simétricos por meio de interações π recíprocas do tipo metal-η2-areno. As unidades dímeras relacionadas entre si através de um plano de reflexão-translação diagonal n, são operadas ao longo da direção cristalográfica [101] originando cadeias através de ligações de hidrogênio não clássicas C-H···(O)COEt envolvendo o grupamento orto C-H do ligante piridina. Estas cadeias por sua vez, relacionam-se entre si por translação na cela elementar através de um segundo tipo de ligação de hidrogênio não-clássica, esta envolvendo átomos de hidrogênio e oxigênio de grupos etoxicarbonilfenil adjacentes na direção cristalográfica [100], resultando um arranjo cristalino supramolecular (2D) estendido paralelo ao plano cristalográfico (011).

Deprotonated 1,3-bis(4-ethoxycarbonylphenyl)triazene reacts with Hg(CH3COO)2 in tetrahydrofurane to give light-yellow crystals of {[HgII(RC6H4NNNC6H4R)2Py]2}n [R = EtOC(O)]. The [HgII(RC6H4NNNC6H4R)2Py] tectons are linked to pairs as centrosymmetric dimers through reciprocal metal-η2-arene π-interactions. The dimeric units - related to each other by a n-glide plane - are linked into chains along to the crystallographic direction [101] through non classical C-H···(O)COEt (hydrogen) bonds involving the ortho C-H group of the pyridine ligand. These chains are related by translation in the unit cell along the direction [100] through another kind of non classical hydrogen bonding, this one involving hydrogen and oxygen atoms of adjacent ethoxycarbonylphenyl groups of the same plane, resulting an extended supramolecular bidimensional (2D) assembling parallel to the crystallographic plane (011).

O novo cloroisopropóxido binuclear de titânio(IV), [{TiCl(OPr i)2(HOPr i )}2(mi-OPr i)2] (1), e o primeiro oxo-cloroalcoolato de vanádio(IV) mononuclear, [VCl(O)(HOPr i)4]Cl (2), foram preparados através da reação entre [Ti(OPr i)4], KOPr i e VCl3 em proporção 2:1:1. Os produtos foram caracterizados por análise elementar, espectroscopia na região do infravermelho, RPE, RMN, espectroscopia eletrônica, medidas de susceptibilidade magnética e difratometria de raios-X (monocristal). A estrutura eletrônica de 1 foi analisada através de cálculos mecânico-quânticos em nível semi-empírico. Esses complexos são precursores em potencial de óxidos homo- e heterometálicos.

The novel binuclear titanium(IV) complex [{TiCl(OPr i)2(HOPr i )}2(mu-OPr i)2], 1, and the first mononuclear vanadyl(IV) chloroalcoholate [VCl(O)(HOPr i)4]Cl, 2, have been prepared from 2:1:1 mixtures of [Ti(OPr i)4], KOPr i and VCl3. Products were characterised by elemental analysis, FTIR, EPR, NMR and electronic spectroscopies, magnetic susceptibility measurements and single crystal X-ray diffractometry. A third product was found to be polynuclear and to contain both titanium and vanadium. Semi-empirical quantum-mechanical calculations were carried out for the evaluation of the electronic structure of 1.

A reação entre (eta5-C5H5)2NbCl2, eta5-C5H5 = Cp, e (Ph)3Sn(SPh), em THF, originou os complexos (eta5-C5H5)2Nb(Cl)( mi-S)Sn(Ph)3(Cl), 1, e (eta5-C5H5)2Nb(S)Cl, 2. Os complexos 1 e 2 foram caracterizados por espectroscopias no IV, de RMN ¹H, RMN 13C, RMN 119Sn, Mössbauer, análise elementar e absorção atômica. Hidrólise de 1 originou a espécie mi-oxo (eta5-C5H5)2Nb(Cl)(mi-O)Sn(Ph)3Cl, 3, que foi caracterizada por espectroscopias no IV, RMN ¹H, RMN 13C, Mössbauer, análise elementar, absorção atômica bem como por cristalografia de raios-X. O complexo 3 cristaliza no grupo de espaço Pca2(1) com a = 17.282(3), b = 18.122(4), c = 17.3269(2), V = 5426.2(16) ų e Z = 8. Estudos adicionais indicaram que os complexos foram formados como resultado da substituição nucleofílica do cloro da ligação nióbio-cloro pelo ligante tiolato seguido da quebra da ligação C-S. A quebra ocorre com um excesso do composto tiolato igual ou maior que 2:1.

Upon reacting (eta5-C5H5)2NbCl2, eta5-C5H5 = Cp, and (Ph)3Sn(SPh), in THF, (eta5-C5H5)2Nb(Cl)(mu-S)Sn(Ph)3(Cl), 1, and (eta5-C5H5)2Nb(S)Cl, 2, were obtained. Complexes 1 and 2 were characterized by IR, ¹H-NMR, 13C-NMR, Mössbauer spectroscopies, elemental analysis as well as by atomic absorption. Hydrolysis of 1 yielded the mu-oxo species, (eta5-C5H5)2Nb(Cl)(mu-O)Sn(Ph)3Cl, 3, which was characterized by IR, ¹H-NMR, 13C-NMR and Mössbauer spectroscopies, elemental analysis, atomic absorption as well as by X-ray crystallography. It crystallizes in the space group Pca2(1) with a = 17.282(3), b = 18.122(4), c = 17.3269(2), V = 5426.2(16) ų, and Z = 8. Additional studies indicated that the complexes were formed as a result of the nucleophilic displacement of the niobium-chloride bond by the thiolate ligand followed by a C-S bond cleavage. The cleavage occurs with an excess of the thiolate compound equal to or greater than 2:1.