Synthesis, Antimicrobial and Antiproliferative Activity of Novel Silver(I) Tris(pyrazolyl)methanesulfonateand 1,3,5-Triaza-7-phosphadamantane Complexes

Five new silver(I) complexes of formulas [Ag(Tpms)] (1), [Ag(Tpms)-(PPh3)] (2), [Ag(Tpms)(PCy3)] (3), [Ag(PTA)][BF4] (4), and [Ag(Tpms)(PTA)] (5) {Tpms = tris(pyrazol-1-yl)methanesulfonate, PPh3 = triphenylphosphane, PCy3 = tricyclohexylphosphane, PTA = 1,3,5-triaza-7-phosphaadamantane) have been synthesized and fully characterized by elemental analyses, H-1, C-13, and P-31 NMR, electrospray ionization mass spectrometry (ESI-MS), and IR spectroscopic techniques. The single crystal X-ray diffraction study of 3 shows the Tpms ligand acting in the N-3-facially coordinating mode, while in 2 and 5 a N2O-coordination is found, with the SO3 group bonded to silver and a pendant free pyrazolyl ring. Features of the tilting in the coordinated pyrazolyl rings in these cases suggest that this inequivalence is related with the cone angles of the phosphanes. A detailed study of antimycobacterial and antiproliferative properties of all compounds has been carried out. They were screened for their in vitro antimicrobial activities against the standard strains Enterococcus faecalis (ATCC 29922), Staphylococcus aureus (ATCC 25923), Streptococcus pneumoniae (ATCC 49619), Streptococcus pyogenes (SF37), Streptococcus sanguinis (SK36), Streptococcus mutans (UA1S9), Escherichia coli (ATCC 25922), and the fungus Candida albicans (ATCC 24443). Complexes 1-5 have been found to display effective antimicrobial activity against the series of bacteria and fungi, and some of them are potential candidates for antiseptic or disinfectant drugs. Interaction of Ag complexes with deoxyribonucleic acid (DNA) has been studied by fluorescence spectroscopic techniques, using ethidium bromide (EB) as a fluorescence probe of DNA. The decrease in the fluorescence of DNA EB system on addition of Ag complexes shows that the fluorescence quenching of DNA EB complex occurs and compound 3 is particularly active. Complexes 1-5 exhibit pronounced antiproliferative activity against human malignant melanoma (A375) with an activity often higher than that of AgNO3, which has been used as a control, following the same order of activity inhibition on DNA, i.e., 3 > 2 > 1 > 5 > AgNO3 >> 4.

Antimicrobial activity of pyrazine and quinoxaline N,N’-dioxide heterocyclic compounds

The nitrogen heterocyclic organic compounds 1,4 dioxide pyrazine and quinoxaline derivatives have been widely studied due to their potential use as synthetic drugs. The thermochemical study of three N,N´-dioxides: 2,3,5-trimethylpyrazine-1,4-dioxide, tetramethylpyrazine-1,4-dioxide and 6-chloro-2,3-dimethilquinoxaline 1,4-dioxide has been recently developed in order to establish relationships among the energetical, structural and reactivity properties [4,5]. Several studies have reported their pharmacological activity, particularly as antimicrobial agents [1,2,3]. It has also been established a relation between energetical and structural properties and biological activity, once these compounds present N – oxide bonds, increasing their oxidative capacity. The present work reports the study of antimicrobial activity for those compounds against the bacteria Geobacillus stearothermophylus, Staphylococcus aureus, Streptococcus agalactiae, Escherichia coli and also against the yeasts Saccharomyces cerevisiae PYCC 4072, Candida albicans PYCC3436T, Candida tropicalis PYCC, Issatchenka Orientalis PYCC. The determination of the minimal inhibitory concentration (MIC), points to an antimicrobial activity and the preliminary results indicate that these compounds may be potential candidates as antimicrobial drugs with clinical, agriculture or food industries applications.

Fungidal and bacterial activity of N,N-dimethyl-4-(2,2,2-trichloro-1-(phenylamino)ethyl)aniline

N,N-dimethyl-4-((phenylamino)methyl)aniline (1) was prepared by condensation of aniline and 4-(dimethylamino)benzaldehyde [1] N,N-dimethyl-4-(2,2,2-trichloro-1-(phenylamino)ethyl)aniline (2) was synthesized by trichloromethylation of the imine (N,N-dimethyl-4-((phenylimino)methyl)aniline (1)) with trichloroacetic anhydride under microwave irradiation [2] (Sheme 1). The present work reports the study of bacterial and yeast activity for the compound 2. The bacteria used in this study are Staphylococcus aureus, Escherichia coli and the yeast are Saccharomyces Cerevisiae Candida albican.The results that we will present are the determination of minimal inhibitory concentration (MIC), by means of microdilution by plate method and the specific growth constants for this microorganism. Further studies are being performed to determine viability and cellular injury with this drug.

Development and biological evaluation of API-ILs based on anti-bacterial and anti-fungal drugs

In recent years Ionic Liquids (ILs) are being applied in life sciences. ILs are being produce with active pharmaceutical drugs (API) as they can reduce polymorphism and drug solubility problems [1] Also ILs are being applied as a drug delivery device in innovative therapies What is appealing in ILs is the ILs building up platform, the counter-ion can be carefully chosen in order to avoid undesirable side effects or to give innovative therapies in which two active ions are paired. This work shows ILs based on ampicillin (an anti-bacterial agent) and ILs based on Amphotericin B. Also we show studies that indicate that ILs based on Ampicillin could reverse resistance in some bacteria. The ILs produced in this work were synthetized by the neutralization method described in Ferraz et. al. [2] Ampicillin anion was combined with the following organic cations 1-ethyl-3-methylimidazolium, [EMIM]; 1-hydroxy-ethyl-3-methylimidazolium, [C2OHMIM]; choline, [cholin]; tetraethylammonium, [TEA]; cetylpyridinium, [C16pyr] and trihexyltetradecylphosphonium, [P6,6,6,14]. Amphotericin B was combined with [C16pyr], [cholin] and 1-metohyethyl-3-methylimidazolium, [C3OMIM]. The ILs-APIs based on ampicillin[2] were tested against sensitive Gram-negative bacteria Escherichia coli ATCC 25922 and Klebsiella pneumonia (clinical isolated), as well as on Gram positive Staphylococcus Aureus ATCC 25923, Staphylococcus epidermidis and Enterococcus faecalis. The arising resistance developed by bacteria to antibiotics is a serious public health threat and needs new and urgent measures. We study the bacterial activity of these compounds against a panel of resistant bacteria (clinical isolated strains): E. coli CTX M9, E. coli TEM CTX M9, E. coli TEM1, E. coli CTX M2, E. coli AmpC Mox2. In this work we demonstrate that is possible to produce ILs from anti-bacterial and anti-fungal compounds. We show here that the new ILs can reverse the bacteria resistance. With the careful choice of the organic cation, it is possible to create important biological and physic-chemical properties. This work also shows that the ion-pair is fundamental in ampicillin mechanism of action.

ß-Lactams: chemical structure, mode of action and mechanisms of resistance

This synopsis summarizes the key chemical and bacteriological characteristics of β-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This review also summarizes the main resistance mechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum β-lactamases and AmpC β-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump β-lactams out of the bacterial cell.

Post-surgical wound infections involving Enterobacteriaceae with reduced susceptibility to ß-lactams in two Portuguese hospitals

The post-surgical period is often critical for infection acquisition. The combination of patient injury and environmental exposure through breached skin add risk to pre-existing conditions such as drug or depressed immunity. Several factors such as the period of hospital staying after surgery, base disease, age, immune system condition, hygiene policies, careless prophylactic drug administration and physical conditions of the healthcare centre may contribute to the acquisition of a nosocomial infection. A purulent wound can become complicated whenever antimicrobial therapy becomes compromised. In this pilot study, we analysed Enterobacteriaceae strains, the most significant gram-negative rods that may occur in post-surgical skin and soft tissue infections (SSTI) presenting reduced β-lactam susceptibility and those presenting extended-spectrum β-lactamases (ESBL). There is little information in our country regarding the relationship between β-lactam susceptibility, ESBL and development of resistant strains of microorganisms in SSTI. Our main results indicate Escherichia coli and Klebsiella spp. are among the most frequent enterobacteria (46% and 30% respectively) with ESBL production in 72% of Enterobacteriaceae isolates from SSTI. Moreover, coinfection occurred extensively, mainly with Pseudomonas aeruginosa and Methicillin-resistant Staphylococcus aureus (18% and 13%, respectively). These results suggest future research to explore if and how these associations are involved in the development of antibiotic resistance.

Real-time rheology of actively growing bacteria

The population growth of a Staphylococcus aureus culture, an active colloidal system of spherical cells, was followed by rheological measurements, under steady-state and oscillatory shear flows. We observed a rich viscoelastic behavior as a consequence of the bacteria activity, namely, of their multiplication and density-dependent aggregation properties. In the early stages of growth (lag and exponential phases), the viscosity increases by about a factor of 20, presenting several drops and full recoveries. This allows us to evoke the existence of a percolation phenomenon. Remarkably, as the bacteria reach their late phase of development, in which the population stabilizes, the viscosity returns close to its initial value. Most probably, this is caused by a change in the bacteria physiological activity and in particular, by the decrease of their adhesion properties. The viscous and elastic moduli exhibit power-law behaviors compatible with the "soft glassy materials" model, whose exponents are dependent on the bacteria growth stage. DOI: 10.1103/PhysRevE.87.030701.

β-Lactams: chemical structure, mode of action and mechanisms of resistance

This synopsis summarizes the key chemical and bacteriological characteristics of β-lactams, penicillins, cephalosporins, carbanpenems, monobactams and others. Particular notice is given to first-generation to fifth-generation cephalosporins. This reviewalso summarizes the main resistancemechanism to antibiotics, focusing particular attention to those conferring resistance to broad-spectrum cephalosporins by means of production of emerging cephalosporinases (extended-spectrum β-lactamases and AmpC β-lactamases), target alteration (penicillin-binding proteins from methicillin-resistant Staphylococcus aureus) and membrane transporters that pump β-lactams out of the bacterial cell.

Aplicação de filmes de suberina na produção de materiais bio-funcionais

Trabalho Final de Mestrado para obtenção do grau de Mestre em Engenharia Química e Biológica

Living bacteria rheology: Population growth, aggregation patterns, and collective behaviour under diferente shear flows

The activity of growing living bacteria was investigated using real-time and in situ rheology-in stationary and oscillatory shear. Two different strains of the human pathogen Staphylococcus aureus-strain COL and its isogenic cell wall autolysis mutant, RUSAL9-were considered in this work. For low bacteria density, strain COL forms small clusters, while the mutant, presenting deficient cell separation, forms irregular larger aggregates. In the early stages of growth, when subjected to a stationary shear, the viscosity of the cultures of both strains increases with the population of cells. As the bacteria reach the exponential phase of growth, the viscosity of the cultures of the two strains follows different and rich behaviors, with no counterpart in the optical density or in the population's colony-forming units measurements. While the viscosity of strain COL culture keeps increasing during the exponential phase and returns close to its initial value for the late phase of growth, where the population stabilizes, the viscosity of the mutant strain culture decreases steeply, still in the exponential phase, remains constant for some time, and increases again, reaching a constant plateau at a maximum value for the late phase of growth. These complex viscoelastic behaviors, which were observed to be shear-stress-dependent, are a consequence of two coupled effects: the cell density continuous increase and its changing interacting properties. The viscous and elastic moduli of strain COL culture, obtained with oscillatory shear, exhibit power-law behaviors whose exponents are dependent on the bacteria growth stage. The viscous and elastic moduli of the mutant culture have complex behaviors, emerging from the different relaxation times that are associated with the large molecules of the medium and the self-organized structures of bacteria. Nevertheless, these behaviors reflect the bacteria growth stage.

A segurança alimentar no consumo de pescado cru com valência para a produção de sushi

Dissertação apresentada para a obtenção do Grau de Mestre em Tecnologia e Segurança Alimentar, pela Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Estudos epidemiológicos entre grupos indígenas de Rondônia: I— Piodermites e portadores inaparentes de Staphylococcus sp. na boca e nariz entre os Suruí e Karitiana

Foram realizadas culturas bacteriológicas a partir de material colhido na boca e nariz entre 38 pacientes indígenas Suruí e 58 Karitiana, no Estado de Rondônia. Entre os Suruí, foi isolado S. aureus em 10 (26,3%) indivíduos e S. epidermidis em 25 (65,8%). Na população Karitiana, S. aureus foi isolado em 21 (36,2%) pacientes e S. epidermidis em 42 (72,4%). Testes de sensibilidade as drogas foram realizados com todas as cepas de S. aureus isoladas. É discutido o papel de portadores inaparentes desta bactéria nas cavidades oral e nasal, assim como alguns aspectos relacionados à sua transmissão e prevalência de piodermites entre populações indígenas.

Estudo da etiologia das pneumopatias agudas da infância através da aspiração pulmonar transtorácica, São Paulo, Brasil

No período de abril de 1979 a julho de 1980 foram estudadas 45 crianças, de ambos os sexos, na faixa etária de 2 meses a 5 anos de idade, selecionadas entre as atendidas no Instituto da Criança "Pedro Alcântara" do Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, e acometidas de pneumopatias agudas. Dos 45 pacientes estudados, a maioria (46,7%) encontrava se na faixa de 2-12 meses de idade e, quanto ao estado nutricional, 42,2% eutróficos e 57,8% desnutridos, variando essa desnutrição do grau I ao grau III. Empregando amostras obtidas por aspiração pulmonar e examinando-as pelo método de coloração de Gram e cultura, foi possível identificar o agente etiológico de 26 (57,7%) pneumonias bacterianas nos 45 casos estudados. A identificação direta pelo método de Gram mostrou-se útil como orientação inicial para antibioticoterapia em 44,4% dos casos. Houve nítida predominância do Streptococcus pneumoniae como agente etiológico bacteriano nas pneumopatias agudas da criança nas várias faixas etárias estudadas seguido do Haemophilus influenzae e o Staphylococcus aureus. O estudo comparativo da cultura do aspirado pulmonar e da hemocultura permitiu maior precisão diagnostica (56,7%), revelando-se a hemocultura positiva em apenas 30,0% dos casos. Não foi constatada nenhuma participação de germes anaeróbios nas pneumopatias da amostragem estudada.

Estudo da suscetibilidade "in vitro" a um novo antimicrobiano (IMIPENEM) de patógenos isolados de pacientes hospitalares em vários centros

O imipenem é um novo antibiótico Beta lactâmico, carbapenêmico, altamente potente e com amplo espectro de atividade antimicrobiana. Com intuito de comprovar a eficácia "in vitro" deste fármaco em patógenos mais freqüentes em nosso meio, descrevem os autores, os resultados das provas de suscetibilidade por discos e/ou a correspondência por provas de diluição para determinação da concentração inibitória mínima (CIM) em 1230 cepas compreendendo 41 diferentes espécies bacterianas recém-isoladas, principalmente de pacientes hospitalares em 5 diferentes centros médicos de Sáo Paulo, Rio de Janeiro e Salvador. Nossos resultados preliminares com o antibiótico, em fase final de experimentação clínica e laboratorial, em nosso meio, foram muito promissores, com 96.79% de cepas suscetíveis pela prova do disco (10 μg de imipenem) e 92,31% de correspondência pela determinação do CIM (concentrações de até 4μg/ml). Das 9 espécies bacterianas mais freqüentemente isoladas, correspondendo a 1008 (82%) das 1230 cepas de nosso material, as sensibilidades pela prova do disco foram de 99% (E. coli), 93% (Pseudomonas aeruginosas), 87% (Staphylococcus aureus), 100% (Klebsiella pneumoniae), 98% (Klebsiella sp) e 100% (Streptococcus faecalis) com boa correspondência pela determinação do CIM até 8μg/ml; e 100% para o anaeróbio Bacteróides sp (CIM até 4μg/ml). Ressaltam os autores a eficácia "in vitro" contra patógenos hospitalares que apresentam elevados índices de resistência à grande maioria de antibióticos como o Pseudomonas aeruginosa e para anaeróbios, notadamente o Bacteróides sp.

Diferenças nas propriedades adesivas de Staphylococcus saprophyticus a células HEp-2 e eritrócitos

S. saprophyticus é freqüentemente isolado de infecções do trato urinário de mulheres jovens e sexualmente ativas. Ao contrário de S. aureus, esta espécie não possui fatores de virulência bem definidos. O objetivo deste estudo é analisar a aderência de S. saprophyticus a células HEp-2 e eritrócitos de carneiro. As amostras foram isoladas a partir da urina de pacientes com infecção urinária. Foram realizados testes de hemaglutinação, aderência a células HEp-2 e a capacidade de carboidratos específicos inibirem as interações entre estes tipos celulares e S. saprophyticus. A maioria das cepas se mostrou hemaglutinante e sensível a inibição da hemaglutinação pela manose (100mM). Foram verificados altos níveis de aderência às células HEp-2. As diferenças em especificidade e nível de aderência do microrganismo a células de HEp-2 e eritrócitos sugerem a participação de diferentes adesinas nos processos de interações celulares.