Doutorado em Doenças Infecciosas

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Navegando Doutorado em Doenças Infecciosas por Assunto "1,10-fenantrolina"

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    Efeito de derivados de 1,10-fenantrolina sobre cepas de Acinetobacter baumannii produtoras de carbapenemases
    (Universidade Federal do Espírito Santo, 2019-10-31) Mendes, Roberta Ferreira Ventura; Nunes, Ana Paula Ferreira; https://orcid.org/; http://lattes.cnpq.br/7851528667690358; https://orcid.org/0000-0002-2075-1579; http://lattes.cnpq.br/5751109105279693; Pereira, Fausto Edmundo Lima; https://orcid.org/; http://lattes.cnpq.br/4065537941002091; Spano, Liliana Cruz; https://orcid.org/0000000262056988; http://lattes.cnpq.br/7451382455806895; Silva, Rodrigo Cayo da; https://orcid.org/0000-0002-0709-6282; http://lattes.cnpq.br/5699739668358897; Resende, Juliana Alves; https://orcid.org/0000000254763754; http://lattes.cnpq.br/8223821041049149
    Therapeutic options are becoming limited for patients infected with Acinetobacter baumannii due to increased resistance to commonly used antimicrobial agents, such as carbapenems. The development of new antimicrobials became a priority. In this sense, the present study aimed to evaluate the effects of 1,10-phenanthroline and its derivatives, fendione, Cu-fendione and Ag-fendione, alone and combined with carbapenems in different strains of A. Baumannii producing carbapenemases. For this purpose were investigated: (i) the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (CBM) of the compounds, meropenem (MPM) and imipenem (IMP); (ii) the effect of combining the compounds with MPM and IMP by checkerboard and time-kill curve; (iii) the effect of combinations in a Galleria mellonella model and (iv) the effect of Ag-fendione in a mouse model. The results obtained by determining MIC and CBM demonstrated excellent antimicrobial activity by the four compounds against all strains (n=26). The mean MIC values of 1.10 phenanthroline, fendione, Cu-fendione and Ag-fendione were 12.98, 1.98, 1.56 and 1.56 μg / ml, respectively. Through the checkerboard, synergistic and additive action was verified in the combinations of compounds with IMP and additivity when combined with MPM. The time-kill curve method showed that combinations containing ½ x MIC of Ag-fendione or Cu-fendione produced an additive effect for 6 hours. It was observed that the combination of MPM with Ag-fendione was able to eradicate bacterial cells. Ag-fendione and Cu-fendione showed bactericidal effect in 6 hours, but it was not dose-dependent. The combination of the compound Ag-fendione with MPM showed statistically significant superiority in relation to the agents alone in a model of G. mellonella. The compound Ag-fendione was able to reduce the infection caused by A. baumannii in a model of infection in mice at a concentration of 75 µg / kg. Treatment with ½ × CMI of 1.10-phenanthroline and its derivatives inhibited approximately 68% of the biomass and 60% of the cell viability of A. baumannii in biofilm. Thus, the results obtained demonstrate the potential of 1,10 phenanthroline, fendione, Cu-fendione and Ag-fendione as drug candidates alone or combined with carbapenemic antimicrobials for A. baumannii.