Modern chemical disinfectants and antiseptics. Part I

Aim. To generalize and systematize information on the properties of modern chemical disinfectants and antiseptic agents (DA and AA).Results and discussion. The review provides generalized and systematized information on the properties of modern chemical DA and AA – alkylating reagents, aldehydes, amides, amidines, bisguanidines, dyes, halogenated reagents, halogens and their complexes, 2-nitrofuran derivatives. The classification of DA and AA by their chemical structure was carried out. The activity spectra, possible application ways and forms of DA and AA were given. Their toxicity and impact on the environment were described as well.Conclusions. On the basis of the analysis carried out it was shown that aldehydes, halogen-active compounds and halogen-containing complexes are modern effective DA and AA with a wide spectrum of biocidal action. Amides, amidines and bisguanidines are characterized by a narrow spectrum of activity. Dyes and 2-nitrofuran derivatives are old-fashioned antiseptics.

From Anti-infective Agents to Cancer Therapy: a Drug Repositioning Study Revealed a New Use for Nitrofuran Derivatives

Background: The progression of ovarian cancer seems to be related to HDAC1, HDAC3 and HDAC6 activity. A possible strategy for improving therapies for treating ovarian carcinoma, minimizing the preclinical screenings, is the repurposing of already approved pharmaceutical products as inhibitors of these enzymes. Objective: This work was aimed to implement a computational strategy for identifying new HDAC inhibitors for ovarian carcinoma treatment among approved drugs. Method: The CHEMBL database was used to construct training, test and decoys sets for performing and validating HDAC1, HDAC3 and HDAC6 3D-QSAR models obtained by using FLAP program. Docking and MD simulations were used in combination with the generated models to identify novel potential HDAC inhibitors. Cell viability assays and Western blot analyses were performed on normal and cancer cells for a direct evaluation of the anti-proliferative activity and an in vitro estimation of HDAC inhibition of the compounds selected through in silico screening. Result: The best quantitative prediction was obtained for the HDAC6 3D-QSAR model. The screening of approved drugs highlighted a new potential use as HDAC inhibitors for some compounds, in particular nitrofuran derivatives, usually known for their antibacterial activity, and frequently used as antimicrobial adjuvant therapy in cancer treatment. Experimental evaluation of these derivatives highlighted a significant antiproliferative activity against cancer cell lines overexpressing HDAC6, and an increase in acetylated alpha-tubulin levels. Conclusion: Experimental results support the hypothesis of a potential direct interaction of nitrofuran derivatives with HDACs. In addition to the possible repurposing of already approved drugs, this work suggests the nitro group as a new zinc binding group, able to interact with the catalytic zinc ion of HDACs.

5-Nitrofuran-2-yl Thiohydrazones as Double Antibacterial Agents Synthesis and In Vitro Evaluation

Background: Applying of "double-drug" strategy to 5-nitrofuran derivatives has been proposed. Methods: A small library of 5-Nitrofuran-2-yl Thiohydrazones was developed, and initial screening demonstrated good activity against bacteria and fungi of ESKAPE panel. Results and Conclusion: The synthesis of the desired thiohydrazones was carried out via condensation of 5-nitrofuran-2-carbaldehyde with thiohydrazides of substituted oxamic acids.

Individualized approach to treatment of children with enuresis based on gender diagnostic research

The article substantiates the possibilities of an individualized approach to the treatment of neurosis-like enuresis based on the study of the gender characteristics of 90 children at the age from 6 to 17 years, among them 66 boys and 24 girls with various clinical options for enuresis. The research has proved that the diagnostic algorithm for examining children with neurosis-like enuresis should involve a bladder ultrasound with determination of the residual volume of urine and a bacteriological test of the urine for pathogenic fl ora with an antibiotic sensitivity test. It has been established that the boys predominantly had the hypotonic type of the bladder (57.58 ± 6.13) %, while among the girls the hypertonic type (58.3 ± 7.28) % prevailed. The author presents a varied approach to the examination and treatment of children with enuresis according to the hypotonic and hypertonic types of the bladder. It allows for the right therapy and increases the effectiveness of patients’ treatment. The application of the specific therapy with the drug nitrofuran derivatives is justified, which has proved its high bioavailability, effectiveness and safety as a monotherapy for bladder infections. Further, to improve the adaptive function of the bladder, improve microcirculation, and reduce hypoxia of detrusor, patients were prescribed 10 % solution of nicoti noyl gamma-aminobutyric acid in the form of ion-galvanic procedures on the lumbosacral spine. After treatment, a “hypotonic” type of bladder was diagnosed in 19 % of boys, 21 % of girls. After treatment, the frequency of enuresis episodes per night was significantly reduced. The frequency of enuresis several times a month, twice as often observed in girls. Twice less often, cases of enuresis were observed from once a month to once every 3—6 months. It is proved that the use of the drug nicotinoyl gamma-aminobutyric acid is effective and promising for the treatment of children with neurosis-like enuresis of the hypotonic type. Key words: individualized approach, children, enuresis, gender differences, nitrofuran derivatives, nicotinoyl gamma-aminobutyric acid, bladder ultrasound

Nitrofurans for External Use (Review)

Introduction. Aspects of the use of nitrofurans for external use (nitrofural, furazolidone and furazidin) are described in the article. Review of current research that is dedicated to development of drugs containing nitrofuran derivatives has been carried out. The prospects for creating dosage forms of furaсillin and furazolidone containing their solid dispersions with polymers are considered.Text. The group of nitrofurans is widely in demand in the modern pharmaceutical market. The most common active ingredients – furacillin, furazolidone and furazidin are represented by various dosage forms for both internal and external use. All nitrofuran derivatives have a wide spectrum of antimicrobial action and a specific mechanism of action on bacterial cells. The low level of development of antimicrobial resistance allows nitrofurans to remain one of the most effective chemotherapeutic groups of antimicrobial compounds for many decades. The review shows a numerous current developments carried out by both Russian and foreign authors about use of furacillin, furadonin and furazidin to develop the composition of new drugs, including combination drugs, as well as promising treatment methods. Currently, on the basis of Sechenov University, research is actively conducted to increase the solubility and dissolution rate of nitrofurans in water using the method of solid dispersions. Also, work is underway to develop the composition and technology of solid (instant) dosage forms granules and tablets, and soft dosage forms gels containing furacillin and furazolidone as active substances.Conclusion. Despite the use of active substances from the nitrofuran group in pharmaceutical practice for more than half a century and their low solubility in water, research on the development of complex drugs for external use and mono-preparations of nitrofurans have not lost their relevance and are actively conducted to this day.

Nitrofurantoin—Microbial Degradation and Interactions with Environmental Bacterial Strains

The continuous exposure of living organisms and microorganisms to antibiotics that have increasingly been found in various environmental compartments may be perilous. One group of antibacterial agents that have an environmental impact that has been very scarcely studied is nitrofuran derivatives. Their representative is nitrofurantoin (NFT)—a synthetic, broad-spectrum antibiotic that is often overdosed. The main aims of the study were to: (a) isolate and characterize new microbial strains that are able to grow in the presence of NFT, (b) investigate the ability of isolates to decompose NFT, and (c) study the impact of NFT on microbial cell properties. As a result, five microbial species were isolated. A 24-h contact of bacteria with NFT provoked modifications in microbial cell properties. The greatest differences were observed in Sphingobacterium thalpophilum P3d, in which a decrease in both total and inner membrane permeability (from 86.7% to 48.3% and from 0.49 to 0.42 µM min−1) as well as an increase in cell surface hydrophobicity (from 28.3% to 39.7%) were observed. Nitrofurantoin removal by selected microbial cultures ranged from 50% to 90% in 28 days, depending on the bacterial strain. Although the isolates were able to decompose the pharmaceutical, its presence significantly affected the bacterial cells. Hence, the environmental impact of NFT should be investigated to a greater extent.

Ambulantna poraba antibiotikov pri otrocih v Sloveniji

Background: Antibiotics are among the most common drugs prescribed in outpatient settings. It is estimated that up to 50 % are prescribed unnecessarily or inappropriately. To plan the actions for optimizing the use of antibiotics, we conducted a national antibiotic consumption study in children aged 0–18 years in the period between 2003 and 2015.Methods: In this national retrospective research we analyzed outpatient antibiotic consumption using ATC/DDD classification. The use of antibiotics was recorded in relation to the pattern of prescription, age, gender and health region.Results: The total consumption of antibiotics decreased by 35 % from 979 to 636 prescriptions per 1000 children/year (PTY) during the whole study period. Te use of all antibiotic classes decreased (except for quinolones and nitrofuran derivatives) by 12.5 %–81 %. In all those years we recorded the highest consumption in children aged 1 to 4 years (2184–1160 PTY). Amoxicillin was the most commonly prescribed antibiotic in children aged 0 to 4 years, penicillin V among 5 to 14 years and co-amoxiclav among adolescents aged 15 to 19 years. In health regions in the northeastern part of Slovenia much more antibiotics were prescribed than in other regions. In 2015, 65 % of prescriptions were prescribed by pediatricians and school medicine specialists, 16 % by physicians without specialization, 14 % by GPs/family doctors and 5 % by other specialists.Conclusions: Despite the decrease in outpatient antibiotic use in children and adolescents in Slovenia, the overall and especially broad-spectrum antibiotic consumption (amoxicillin with clavulanic acid, azithromycin and second/third generation cephalosporins) is still too high. It is necessary to strengthen activities to reduce prescribing, particularly for acute (upper) respiratory tract infections.