Impact of Human Serum Proteins on Susceptibility of Acinetobacter baumannii to Cefiderocol: role of iron transport

Cefiderocol is a siderophore antibiotic that co-opts iron transporters to facilitate cell entry. We show that genes related to iron uptake systems and resistance to β-lactams in Acinetobacter baumannii have altered expression levels in the presence of human serum, human serum albumin, or human pleural fluid. Cefiderocol MICs are also raised in the presence of the mentioned fluids. Clinical response in A. baumannii infections may be related to the interplay of these human factors.

Bioactivities of Phenolic Compounds from Kiwifruit and Persimmon

Fruit used in the common human diet in general, and kiwifruit and persimmon particularly, displays health properties in the prevention of heart disease. This study describes a combination of bioactivity, multivariate data analyses and fluorescence measurements for the differentiating of kiwifruit and persimmon, their quenching and antioxidant properties. The metabolic differences are shown, as well in the results of bioactivities and antioxidant capacities determined by ABTS, FRAP, CUPRAC and DPPH assays. To complement the bioactivity of these fruits, the quenching properties between extracted polyphenols and human serum proteins were determined by 3D-fluorescence spectroscopy studies. These properties of the extracted polyphenols in interaction with the main serum proteins in the human metabolism (human serum albumin (HSA), α-β-globulin (α-β G) and fibrinogen (Fgn)), showed that kiwifruit was more reactive than persimmon. There was a direct correlation between the quenching properties of the polyphenols of the investigated fruits with serum human proteins, their relative quantification and bioactivity. The results of metabolites and fluorescence quenching show that these fruits possess multiple properties that have a great potential to be used in industry with emphasis on the formulation of functional foods and in the pharmaceutical industry. Based on the quenching properties of human serum proteins with polyphenols and recent reports in vivo on human studies, we hypothesize that HSA, α-β G and Fgn will be predictors of coronary artery disease (CAD).

Interaction between Antifungal Isoxazolo[3,4-b]Pyridin 3(1H)-One Derivatives and Human Serum Proteins Analyzed with Biomimetic Chromatography and QSAR Approach

The development of effective, nontoxic antifungal agents is one of the most important challenges for medicinal chemistry. A series of isoxazolo [3,4-b]pyridine-3(1H)-one derivatives previously synthesized in our laboratory demonstrated promising antifungal properties. The main goal of this study was to investigate their retention behavior in a human serum proteins-high-performance liquid chromatography (HSA-HPLC) system and explore the molecular mechanism of HSA-isoxazolone interactions using a quantitative structure–retention relationship (QSRR) approach. In order to realize this goal, multiple linear regression (MLR) modeling has been performed. The proposed QSRR models presented correlation between experimentally determined lipophilicity and computational theoretical molecular descriptors derived from Dragon 7.0 (Talete, Milan, Italy) software on the affinity of isoxazolones to HSA. The calculated plasma protein binding (PreADMET software) as well as chromatographic lipophilicity (logkw) and phospholipophilicity (CHIIAM) parameters were statistically evaluated in relation to the determined experimental HAS affinities (logkHSA). The proposed model met the Tropsha et al. criteria R2 > 0.6 and Q2 > 0.5 These results indicate that the obtained model can be useful in the prediction of an affinity to HSA for isoxazolone derivatives and they can be considered as an attractive alternative to HSA-HPLC experiments.