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The increasing antibiotic resistance is a clinical problem worldwide. Numerous Gram-negative bacteria have already become resistant to the most widely used class of antibacterial drugs, β-lactams. One of the main mechanisms is inactivation of β-lactam antibiotics by bacterial β-lactamases. Appearance and spread of these enzymes represent a continuous challenge for the clinical treatment of infections and for the design of new antibiotics and inhibitors. Drug repurposing is a prospective approach for finding new targets for drugs already approved for use. We describe here the inhibitory potency of known detoxifying antidote 2,3-dimercaptopropane-1-sulfonate (unithiol) against metallo-β-lactamases. Unithiol acts as a competitive inhibitor of meropenem hydrolysis by recombinant metallo-β-lactamase NDM-1 with the K_I of 16.7 µM. It is an order of magnitude lower than the K_I for l-captopril, the inhibitor of angiotensin-converting enzyme approved as a drug for the treatment of hypertension. Phenotypic methods demonstrate that the unithiol inhibits natural metallo-β-lactamases NDM-1 and VIM-2 produced by carbapenem-resistant K. pneumoniae and P. aeruginosa bacterial strains. The 3D full atom structures of unithiol complexes with NDM-1 and VIM-2 are obtained using QM/MM modeling. The thiol group is located between zinc cations of the active site occupying the same place as the catalytic hydroxide anion in the enzyme–substrate complex. The sulfate group forms both a coordination bond with a zinc cation and hydrogen bonds with the positively charged residue, lysine or arginine, responsible for proper orientation of antibiotics upon binding to the active site prior to hydrolysis. Thus, we demonstrate both experimentally and theoretically that the unithiol is a prospective competitive inhibitor of metallo-β-lactamases and it can be utilized in complex therapy together with the known β-lactam antibiotics. Full article

The effectiveness of an amphoteric cryogel (AAC) as an oral sorbent (enerosorbent) for the treatment of acute poisoning of small animals (rats) with heavy metals (HMs) was studied in in vivo experiments. The morphological structure of the cryogel was examined using scanning electron microscopy/energy-dispersive X-ray analysis and confocal microscopy. The use of the cryogel in the treatment of rats administered an LD₅₀ dose of Cd(NO₃)₂, CsNO₃, Sr(NO₃)₂, or HgCl₂ in aqueous solution showed their high survival rate compared to the control group, which did not receive such treatment. The histological and chemical analysis of internal tissues and the biochemical analysis of the blood of the experimental animals showed the effectiveness of the cryogel in protecting the animals against the damaging effect of HMs on the organism comparable with unithiol, a chelating agent based on 2,3-dimercapto-1-propane sulfonic acid sodium salt (DMPS) approved for the treatment of acute poisoning with some heavy metals. Full article

The analysis of total vitamin C content in food is most frequently performed by reducing dehydroascorbic acid to ascorbic acid, which is then assayed with the technique of high-performance liquid chromatography combined with spectrophotometric detection. Tris(2-carboxyethyl)phosphine is currently the only agent in use that efficiently reduces dehydroascorbic acid at pH < 2. Therefore, there is a continued need to search for new reducing agents that will display a high reactivity and stability in acidic solutions. The objective of the study was to verify the applicability of unithiol and tris(hydroxypropyl)phosphine for a reducing dehydroascorbic acid in an extraction medium with pH < 2. The conducted validation of the newly developed method of determining the total content of vitamin C using tris(hydroxypropyl)phosphine indicates its applicability for food analysis. The method allows obtaining equivalent results compared to the method based on the use of tris(2-carboxyethyl)phosphine. The low efficiency of dehydroascorbic acid reduction with the use of unithiol does not allow its application as a new reducing agent in vitamin C analysis. Full article