Molecular Insights into an Antibiotic Enhancer Action of New Morpholine-Containing 5-Arylideneimidazolones in the Fight against MDR Bacteria.

In the search for an effective strategy to overcome antimicrobial resistance, a series of new morpholine-containing 5-arylideneimidazolones differing within either the amine moiety or at position five of imidazolones was explored as potential antibiotic adjuvants against Gram-positive and Gram-negative bacteria. Compounds (7-23) were tested for oxacillin adjuvant properties in the Methicillin-susceptible S. aureus (MSSA) strain ATCC 25923 and Methicillin-resistant S. aureus MRSA 19449. Compounds 14-16 were tested additionally in combination with various antibiotics. Molecular modelling was performed to assess potential mechanism of action. Microdilution and real-time efflux (RTE) assays were carried out in strains of K. aerogenes to determine the potential of compounds 7-23 to block the multidrug efflux pump AcrAB-TolC. Drug-like properties were determined experimentally. Two compounds (10, 15) containing non-condensed aromatic rings, significantly reduced oxacillin MICs in MRSA 19449, while 15 additionally enhanced the effectiveness of ampicillin. Results of molecular modelling confirmed the interaction with the allosteric site of PBP2a as a probable MDR-reversing mechanism. In RTE, the compounds inhibited AcrAB-TolC even to 90% (19). The 4-phenylbenzylidene derivative (15) demonstrated significant MDR-reversal "dual action" for ß-lactam antibiotics in MRSA and inhibited AcrAB-TolC in K. aerogenes. 15 displayed also satisfied solubility and safety towards CYP3A4 in vitro.

From high oleic vegetable oils to hydrophobic starch derivatives: II. Physicochemical, processing and environmental properties.

Medium-substituted esters of starch and higher fatty acids, structurally identified in the first part of paper were subjected to further analyses, mainly to check application potential. In order to determine the possibility of using the esters in the packaging industry, the glycerol-plasticized starch esters were extruded on a single screw extruder in the form of a film. The mechanical properties tests consisted of tensile and tear strength. Hydrophobicity, water absorption and oil absorption were checked as the processing and functional properties. Environmental tests, such as phytotoxicity on monocotyledonous and dicotyledonous plants and biodegradability in soil under strictly controlled conditions of the vegetation hall were carried out. Esterification increased the hydrophobicity of the starch and the tensile and tear strength, without losing important environmental features such as biodegradability and non-toxicity. The obtained polymer materials give hope for their use in the production of new ecofriendly and biodegradable packaging.