Antimicrobial compositions and uses
A composition, coating composition technology, applied in the direction of drug combination, application, compound of elements of group 4/14 of the periodic table, etc., can solve the problem of unspecified utility and the like
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Embodiment 1
[0056] This example relates to the synthesis of thiophenones. Compound codes (eg Thio101) correspond to those described in Table 1.
[0058] (E)-5-bromomethylenethiophen-2(5H)-one and (Z)-5-bromomethylenethiophen-2(5H)-one. Acetyl bromide (0.5 mL) was added dropwise to 5-formyl-2-methoxythiophene at 0 °C 1 (142mg) CDCl 3 (1.0 mL) solution. The mixture was stirred at 0°C for 1.5 hours, then evaporated. The crude product was purified by flash chromatography using hexane / ethyl acetate (5:1) as eluent. Yield of (E)-5-bromomethylenethiophen-2(5H)-one: 9 mg. Yield of (Z)-5-bromomethylenethiophen-2(5H)-one: 86 mg. The compounds were characterized by mass spectrometry and NMR.
[0059] Thio103
[0060] (Z)-5-Chloromethylenethiophen-2(5H)-one. Acetyl chloride (2 mL) was added to 5-formyl-2-methoxythiophene 1 (142mg). The mixture was stirred overnight at room temperature and then evaporated. The crude product was purified by flash chromatography...
Embodiment 2a
[0100] This example illustrates the effect of thiophenones on biofilm formation of various bacteria. Biofilm formation was measured according to the static biofilm model and the vibrating biofilm model, and it was found that various thiophenones tested either inhibited or prevented biofilm formation.
[0101] According to the static biofilm model, the specified thiophene 200 μmol / L was dissolved in 500 μl absolute ethanol and applied to the wells of a standard 24-well microtiter plate. Ethanol was evaporated from the wells in a laminar flow sterile bench at room temperature, leaving a coating of thiophenone in the wells. Bacterial samples are then added to the wells and incubated for a given period of time. After incubation, the percentage of bacteria remaining was assessed by safranin staining of the biofilm. Bound safranin was released by acetic acid and optical density was measured in a Synergy HT Multi-Detection Microplate Reader and compared to controls. The results ar...
Embodiment 2b
[0110] This example illustrates the effect of additional thiophenes on biofilm formation and planktonic growth of various bacteria.
[0111] Planktonic growth was determined in "low binding plates" where bacteria formed the least amount of biofilm. Quantities were determined by optical density measurements at 600 nm.
[0112] S. epidermidis biofilm formation was measured in static cultures in microtiter plate wells, or according to the Calgary method (The Calgary biofilm devices: New technology for rapid determination of antibiotic susceptibilities of bacterial biofilms. Ceri et al., J Clin Microbiol 1999:37:1771-1776) measured biofilm formation of Vibrio harveyi (V. harveyi) in static cultures on "peggs". In both cases, safranin staining was used and optical density was measured at 530 nm to quantify biofilm mass.
[0113] Thio401
[0114]
[0115] (Z)-4-((5-(bromomethylene)-2-oxo-2,5-dihydrothiophen-3-yl)methoxy)-4-oxobutanoic acid
[0116] The compound was synthesi...
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