Given the extreme importance of the current pandemic caused by COVID-19, and as scientists agree there is no identified pharmacological treatment, where possible, therapeutic alternatives are raised through drug repositioning. This paper presents a selection of studies involving drugs from different pharmaceutical classes with activity against SARS-CoV-2 and SARS-CoV, with the potential for use in the treatment of COVID-19 disease.
The tridentate Schiff base [(2-(imidazol-4-yl)ethyl)(1-methylimidazol-2-yl)methyl)imine (HISMIMI) and its reduced form HISMIMA were synthesized and characterized, as well their mononuclear cis-dihalo copper(II) complexes 1 and 2, respectively. In addition, the dinuclear [CuII(mu-OH)2CuII](2+) complexes (3) and (4) obtained from complexes 1 and 2, respectively, were also isolated and characterized by several physicochemical techniques, including magnetochemistry, electrochemistry, and EPR and UV-vis spectroscopies. The crystal structures of 1 and 2 were determined by X-ray crystallography and revealed two neutral complexes with their tridentate chelate ligands meridionally coordinated. Completing the coordination spheres of the square-pyramidal structures, a chloride ion occupies the apical position and another is bonded in the basal plane. In addition, complexes 1 and 2 were investigated by infrared, electronic, and EPR spectroscopies, cyclic voltammetry, and potentiometric equilibrium studies. The hydrolytic activity on phosphate diester cleavage of 1 and 2 was investigated utilizing 2,4-BDNPP as substrate. These experiments were carried out at 50 degrees C, and the data treatment was based on the Michaelis-Menten approach, giving the following kinetic parameters (complex 1/complex 2): vmax (mol L(-1) s(-1))=16.4x10(-9)/7.02x10(-9); KM (mol L(-1))=17.3x10(-3)/3.03x10(-3); kcat (s(-1))=3.28x10(-4)/1.40x10(-4). Complex 1 effectively promoted the hydrolytic cleavage of double-strand plasmid DNA under anaerobic and aerobic conditions, with a rate constant of 0.28 h(-1) for the decrease of form I, which represents about a 10(7) rate increase compared with the estimated uncatalyzed rate of hydrolysis.
Introduction: Infections caused by methicillin-resistant Staphylococcus aureus (MRSA) have become common in hospitals and the community environment, and this wide resistance has limited patient treatment. Clindamycin (CL) represents an important alternative therapy for infections caused by S. aureus. Antimicrobial susceptibility testing using standard methods may not detect inducible CL resistance. This study was performed to detect the phenotypes of resistance to macrolides-lincosamides-streptogramin B (MLS B ) antibiotics, including CL, in clinical samples of S. aureus from patients at a tertiary hospital in Santa Maria, State of Rio Grande do Sul, Brazil. Methods: One hundred and forty clinical isolates were submitted to the disk diffusion induction test (D-test) with an erythromycin (ER) disk positioned at a distance of 20mm from a CL disk. The results were interpreted according to the recommendations of the Clinical and Laboratory Standards Institute (CLSI). Results: In this study, 29 (20.7%) of the 140 S. aureus samples were resistant to methicillin (MRSA), and 111 (79.3%) were susceptible to methicillin (MSSA). The constitutive resistance phenotype (cMLS B ) was observed in 20 (14.3%) MRSA samples and in 5 (3.6%) MSSA samples, whereas the inducible resistance phenotype (iMLS B ) was observed in 3 (2.1%) MRSA samples and in 8 (5.8%) MSSA samples. Conclusions: The D-test is essential for detecting the iMLS B phenotype because the early identifi cation of this phenotype allows clinicians to choose an appropriate treatment for patients. Furthermore, this test is simple, easy to perform and inexpensive.
Objective To analyze the profile of patients with microorganisms resistant to carbapenems, and the prevalence of the enzyme Klebsiella pneumoniae carbapenemase in interobacteriaceae.Methods Retrospective descriptive study. From the isolation in bacteriological tests ordered by clinicians, we described the clinical and epidemiological characteristics of patients with enterobacteria resistants to carbapenems at a university hospital, between March and October 2013.Results We included 47 isolated patients in this study, all exhibiting resistance to carbapenems, including 9 patients who were confirmed as infected/colonized with K. pneumoniae carbapenemase. Isolation in tracheal aspirates (12; 25.5%) predominated. The resistance to ertapenem, meropenem, and imipenem was 91.5%, 83.0% and 80.0%, respectively. Aminoglycosides was the class of antimicrobials that showed the highest sensitivity, 91.5% being sensitive to amikacin and 57.4% to gentamicin.Conclusion The K. pneumoniae carbapenemase was an important agent in graun isotaling in hospital intection. The limited therapeutic options emphasize the need for rapid laboratory detection, as well as the implementation of measures to prevent and control the spread of these pathogens.
Recebido em 20/4/07; aceito em 3/12/07; publicado na web em 24/7/08 COMPOSITION AND ANTIBACTERIAL ACTIVITY OF THE ESSENTIAL OILS OF Senecio crassiflorus var. crassiflorus. The essential oils of leaves, aerial and underground stems of Senecio crassiflorus var. crassiflorus were extracted by hydrodistillation and their analyses were performed by GC/MS. Qualitative and quantitative differences have been found between the analyzed parts. The main compounds of the essentials oils of the leaves were found to be oxygenated sesquiterpenes, while the oils from the aerial and underground stems showed sesquiterpene hydrocarbons as major constituents. Furthermore, the essential oils were tested against Staphylocccus aureus, Escherichia coli, Pseudomonas aeruginosa and Bacillus cereus. The essential oil of the leaves was shown to be the most active.
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