Antimicrobial activity of quinoxaline 1,4-dioxide and three derivatives

O presente trabalho descreve o estudo da actividad e antimicrobiana de quarto derivados da quinoxalina N,N-dióxido: quinoxalina 1,4-dióxido, 2-metilquinoxalina 1,4- dióxido, 6-cloro-2,3-dimetilquinoxalina 1,4-dióxido e 3-benzoil-2-metilquinoxalina 1,4- dióxido contra as estirpes bacterianas Geobacillus stearothermophilus ATCC 10149, Escherichia coli ATCC 25922, Escherichia coli HB101, Escherichia coli (blaTEM, blaCTX-M) e Salmonella (blaCTX-M), assim como contra a estirpe de levedura Saccharomyces cerevisiae PYCC 4072. A determinação da concentração mínima inibitória (MIC) foi realizada pelo método de diluição. Os valores de MIC’s foram estimados para cada composto e estirpe. Os resultados obtidos sugerem potenciais novas drogas para quimioterapia.

Antimicrobial and cytotoxic assessment of marine cyanobacteria - synechocystis and synechococcus

Aqueous extracts and organic solvent extracts of isolated marine cyanobacteria strains were tested for antimicrobial activity against a fungus, Gram-positive and Gram-negative bacteria and for cytotoxic activity against primary rat hepatocytes and HL-60 cells. Antimicrobial activity was based on the agar diffusion assay. Cytotoxic activity was measured by apoptotic cell death scored by cell surface evaluation and nuclear morphology. A high percentage of apoptotic cells were observed for HL-60 cells when treated with cyanobacterial organic extracts. Slight apoptotic effects were observed in primary rat hepatocytes when exposed to aqueous cyanobacterial extracts. Nine cyanobacteria strains were found to have antibiotic activity against two Gram-positive bacteria, Clavibacter michiganensis subsp. insidiosum and Cellulomonas uda. No inhibitory effects were found against the fungus Candida albicans and Gram-negative bacteria. Marine Synechocystis and Synechococcus extracts induce apoptosis in eukaryotic cells and cause inhibition of Gram-positive bacteria. The different activity in different extracts suggests different compounds with different polarities.

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.

Protein-ligand docking study: diterpenes from Juniperus brevifolia as anticancer and antimicrobial agentes

REDCAT: Natural Products and related Redox Catalysts: Basic Research and Applications in Medicine and Agriculture, Aveiro, 25-27 Novembro de 2012.

Genetic diversity and epidemiology of antimicrobial resistant Streptococcus pneumoniae isolates

Dissertation presented to obtain a Ph.D. degree in Biology, speciality in Microbiology, by Universidade Nova de Lisboa, Faculdade de Ciências e Tecnologia

Antimicrobial resistance and plasmid detection in strains of the Bacteroides fragilis group

Resistant populations of the Bacteroides fragilis group bacteria (two reference ones and two isolated from human and Callithrix penicillata marmoset) were obtained by the gradient plate technique, to clindamycin, penicillin G, metronidazole and mercuric chloride. All the four tested strains were originaly susceptible to the four antimicrobial drugs at the breakpoint used in this study. MICs determination for the four cultures gave constant values for each antimicrobial, on the several steps by the gradient plate technique. The intestinal human B. fragilis strains showed three DNA bands, that could be representative of only two plasmids in the closed covalently circular (CCC) form with molecular weights of approximately 25 and 2.5 Md. The results do not permit an association between the presence of plasmid in the human strain with the susceptibility to the studied drugs. The four strains were ß-lactamase negative in the two methods used, and no particular chromosomal genetic resistance marker was demonstred. The resistance (MIC) observed, after contact with penicillin G and mercuric chloride, were two-fold in the four tested strains

Unravelling novel modes of antimicrobial action

Dissertation presented to obtain the Ph.D. degree in Biochemistry at the Instituto de Tecnologia Química e Biológica, Universidade Nova de Lisboa

Epidemiology and antimicrobial resistance of B. fragilis group organisms isolated from clinical specimen and human intestinal microbiota

Epidemiological aspects and the antimicrobial susceptibility profile of the Bacteroides fragilis group isolated from clinical and human intestinal specimens were examined in this study. B. fragilis group strains were isolated from 46 (37%) of 124 clinical specimens and the source of the samples was: Blood culture (3), intraabdominal infection (27), brain abscess (2), soft tissue infection (17), respiratory sinus (3), pleural aspirate (9), breast abscess (3), surgical infected wound (22), pelvic inflammatory disease (22), chronic otitis media (9) and miscellaneous (7). Intraabdominal and soft tissue infections were responsible for more than half of the clinical isolates. Susceptibility to penicillin, cefoxitin, tetracycline, metronidazole, chloramphenicol and clindamycin was examined. All isolates were susceptible to metronidazole and chloramphenicol. For clindamycin and cefoxitin the resistance rates observed were 21.7% and 10.9% respectively. Susceptibility profiles varied among the different species tested. A total of 37 species of B. fragilis group isolated from intestinal microbiota of individuals who had no antimicrobial therapy for at least 1 month before the sampling was also examined. All strains were also susceptible to chloramphenicol and motronidazole and the resistance rates to clindamycin and cefoxitin were 19.4% and 5.4% respectively. A few institutions, in Brazil, have monitored the antimicrobial susceptibility of B. fragilis group strains isolated from anaerobic infections. The resistance rates to cefoxitin and clindamycin and the variation in susceptibility patterns among the species isolated in this study emphasize the need for monitoring of susceptibility patterns of B. fragilis group organisms isolated, especially at our University Hospitals.

Genetic diversity and antimicrobial resistance of enterococcal isolates from Southern region of Brazil

In the present study, a total of 455 enterococcal isolates, recovered from patients living in the city of Porto Alegre, State of Rio Grande do Sul, Brazil, during the period from July 1996 to June 1997, were identified to the species level by conventional biochemical and microbiological tests, and assayed for their susceptibilities to antimicrobial agents. The genetic diversity of antimicrobial resistant strains was evaluated by pulsed-field gel electrophoresis (PFGE) analysis of SmaI restricted chromosomal DNA. The most frequent species was Enterococcus faecalis (92.8%). Other species identified were: E. faecium (2.9%), E. gallinarum (1.5%), E. avium (1.1%), E. hirae (0.7%), E. casseliflavus (0.4%), E. durans (0.4%) and E. raffinosus (0.2%). The overall prevalence of isolates with high-level resistance (HLR) to aminoglycosides was 37.8%. HLR to gentamicin was found in 24.8%. No strains with acquired resistance to vancomycin were found. PFGE analysis showed the predominance of clonal group A, comprising strains isolated from different clinical specimens obtained from patients in three hospitals. These results suggest intra and inter-hospital dissemination of one predominant clonal group of E. faecalis isolates with HLR to gentamicin in the hospitals included in this study.

Evaluation of the in vitro activity of six antimicrobial agents against Neisseria gonorrhoeae

Use of antimicrobials for the treatment of gonorrhea started in 1930 with the utilization of sulfonamides. With the years other drugs were used for its treatment such as penicillin, tetracycline, spectinomycin, and others. Although highly specific in the beginning, these drugs, with time did not show anymore the expected therapeutic results because of aspects of chromosomal and plasmid-mediated resistance. The purpose of this study was to evaluate the susceptibility of Neisseria gonorrhoeae strains to six drugs used for its treatment (penicillin, tetracycline, cefoxitin, thiamphenicol, spectinomycin and ofloxacin) by the determination of minimal inhibitory concentrations of these drugs. We concluded that drugs, such as cefoxitin, thiamphenicol and spectinomycin still are excellent pharmacological agents for the treatment of gonorrhea. Penicillin, although still efficient, needs more attention regarding its use, as well as ofloxacin, because of the emergence of resistant strains. Tetracycline and its derivatives should be strongly contraindicated for the treatment of gonorrhea.

A Rat Model of Diabetic Wound Infection for the Evaluation of Topical Antimicrobial Therapies

Diabetes mellitus is an epidemic multisystemic chronic disease that frequently is complicated by complex wound infections. Innovative topical antimicrobial therapy agents are potentially useful for multimodal treatment of these infections. However, an appropriately standardized in vivo model is currently not available to facilitate the screening of these emerging products and their effect on wound healing. To develop such a model, we analyzed, tested, and modified published models of wound healing. We optimized various aspects of the model, including animal species, diabetes induction method, hair removal technique, splint and dressing methods, the control of unintentional bacterial infection, sampling methods for the evaluation of bacterial burden, and aspects of the microscopic and macroscopic assessment of wound healing, all while taking into consideration animal welfare and the '3Rs' principle. We thus developed a new wound infection model in rats that is optimized for testing topical antimicrobial therapy agents. This model accurately reproduces the pathophysiology of infected diabetic wound healing and includes the current standard treatment (that is, debridement). The numerous benefits of this model include the ready availability of necessary materials, simple techniques, high reproducibility, and practicality for experiments with large sample sizes. Furthermore, given its similarities to infected-wound healing and treatment in humans, our new model can serve as a valid alternative for applied research.

Clonal types and antimicrobial resistance profiles of methicillin-resistant Staphylococcus aureus isolates from hospitals in south Brazil

In the present study were evaluated the DNA macrorestriction profile and SCCmec types for nine multi-resistant MRSA selected. Also antimicrobial susceptibility testing by disk diffusion method was evaluated for 68 MRSA isolates against 12 antimicrobial agents. The isolates were recovered from blood culture collected from hospitalized patients in three hospitals of Porto Alegre, Brazil. PFGE and PCR for mecA and SCCmec I, II, III, IV types genes were done on selected nine isolates with susceptibility only to vancomycin, teicoplanin and linezolid. Two clone profiles, with five subtypes, were demonstrated among multi-resistant MRSA analyzed. Eight isolates showed harbor SCCmec type III and one isolate was not typeable. The knowledge of SCCmec type, clone and antimicrobial profiles among S. aureus is essential mainly to prevention and control of dissemination of the antimicrobial resistance.