Pronounced Antimicrobial Activity Research Articles

Genome-based classification of Streptomyces pinistramenti sp. nov., a novel actinomycete isolated from a pine forest soil in Poland with a focus on its biotechnological and ecological properties.

A genomic-based polyphasic study was undertaken to establish the taxonomic status and biotechnological and ecological potential of a Streptomyces strain, isolate SF28T, that was recovered from the litter layer in a Polish Pinus sylvestris forest. The isolate had morphological characteristics and chemotaxonomic properties consistent with its classification in the genus Streptomyces. It formed long straight chains of spores with smooth surfaces, contained LL-diaminopimelic acid, glucose and ribose in whole-organism hydrolysates, produced major proportions of straight, iso- and anteiso- fatty acids, hexa- and octa-hydrogenated menaquinones with nine isoprene units and had a polar lipid pattern composed of diphosphatidylglycerol, phosphatidylethanolamine, phosphatidylmethylethanolamine, glycophospholipids and three uncharacterized components. Phylogenetic trees prepared using 16S rRNA gene and multilocus gene sequences of conserved housekeeping genes showed that the isolate formed a branch that was loosely associated with the type strains of several validly published Streptomyces species. A draft genome generated for the isolate was rich in natural product-biosynthetic gene clusters with the potential to produce new specialised metabolites, notably antibiotics, and stress related genes which provide an insight into how it may have become adapted to the harsh conditions that prevail in acidic forest soils. A phylogenomic tree based on the genomes of the isolate and its phylogenetic neighbours confirmed that it formed a distinct lineage well separated from its closest evolutionary relatives. The isolate shared low average nucleotide identity and digital DNA:DNA hybridization values with its phylogenomic neighbours and was also distinguished from them using a combination of cultural and micromorphological properties. Given this wealth of taxonomic data it is proposed that isolate SF28T (= DSM 113360T = PCM 3163T) be classified in the genus Streptomyces as Streptomyces pinistramenti sp. nov. The isolate showed pronounced antimicrobial activity, especially against fungal plant pathogens.

Antimicrobial activity of toothpastes against early childhood caries

Objective: assessing antimicrobial activity of toothpastes with different ingredient composition recommended for infants and toddlers. Materials and Methods. The study object was dental plaque of children with decompensated form of caries under the age of 3 years old. Seven toothpastes with different composition designed for early childhood were studied. Identification of detected microorganisms was carried out via mass spectrometry. Antibacterial activity was determined by agar diffusion and serial dilution methods. Results. Toothpastes containing xylitol, lactic enzymes and ingredients of medicinal herbs exhibited the absence of a microbial growth inhibition zone. Fluoride toothpastes were active against all tested microorganisms, and the final fluoride inhibitory concentration was 0.00016-0.0025%, depending on the fluoride concentration in the toothpaste. Conclusion. The least pronounced antimicrobial activity was detected in complex toothpastes with lactic enzymes and ingredients of medicinal herbs, as well as in samples with xylitol. Simple toothpastes with organic and inorganic fluorine compounds demonstrated the best bactericidal effect.

Systematic comparison of activity and mechanism of antimicrobial peptides against nosocomial pathogens

The World Health Organisation has deemed several multi-drug resistant (MDR) nosocomial bacterial pathogens to be of significant threat to human health. A stark increase in morbidity, mortality and the burden to healthcare systems around the world can be attributed to the development of resistance in these bacteria. Accordingly, alternative antimicrobial agents have been sought as an attractive means to combat MDR pathogens, with one such example being antimicrobial peptides (AMPs). Given the reported activity of AMPs, including Pardaxin, MSI-78, dermaseptin-PC (DMPC) and Cecropin B, it is important to understand their activities and modes of action against bacteria for further AMP design. In this study, we compared these AMPs against a panel of nosocomial bacterial pathogens, followed by detailed mechanistic studies. It was found that Pardaxin (1–22) and MSI-78 (4–20) displayed the most pronounced antimicrobial activity against the tested bacteria. The mechanistic studies by membrane permeability and molecular dynamics simulation further confirmed the strong membrane interaction and structure of Pardaxin (1–22) and MSI-78 (4–20), which contributed to their potent activity. This study demonstrated a structure and activity guidance for further design of Pardaxin (1–22) and MSI-78 (4–20) as therapeutics against MDR pathogens. The different effects of DMPC (1–19) and Cecropin B (1–21) on membrane integrity and phospholipid membrane interactions provided critical information for the rational design of next-generation analogues with specificity against either Gram-negative or Gram-positive bacteria.

Synthesis approach-dependent antiviral properties of silver nanoparticles and nanocomposites.

Numerous viral infections are common among humans, and some can lead to death. Even though conventional antiviral agents are beneficial in eliminating viral infections, they may lead to side effects or physiological toxicity. Silver nanoparticles and nanocomposites have been demonstrated to possess inhibitory properties against several pathogenic microbes, including archaea, bacteria, fungi, algae, and viruses. Its pronounced antimicrobial activity against various microbe-mediated diseases potentiates its use in combating viral infections. Notably, the appropriated selection of the synthesis method to fabricate silver nanoparticles is a major factor for consideration as it directly impacts antiviral efficacy, level of toxicity, scalability, and environmental sustainability. Thus, this article presents and discusses various synthesis approaches to produce silver nanoparticles and nanocomposites, providing technological insights into selecting approaches to generate antiviral silver-based nanoparticles. The antiviral mechanism of various formulations of silver nanoparticles and the evaluation of its propensity to combat specific viral infections as a potential antiviral agent are also discussed.Graphical abstract

Improving the synthesis of hemin derivatives and their effect on bacterial biofilms

The emergence of antibiotic-resistant bacterial strains has recently resulted in a large focus on designing new antimicrobial agents, including those based on natural compounds. We have previously synthesized two disubstituted arginine-containing derivatives of hemin (HD) (4) and (5) that demonstrated pronounced antimicrobial activity against planktonic cells in vitro [1, 2]. These HDs are leading and promising for the creation of antibacterial agents on their basis. This research is aimed at improving the synthesis of HDs (4) and (5) to increase their yield, simplify the process and minimize the side reactions, as well as to establish their antimicrobial and destructive effect on biofilms, including those consisting of antibiotic-resistant bacteria. As a result, we were able to increase the yields of the protected dipeptide of ZArg(Z[Formula: see text]SerNH2 (3) and the corresponding HD (4) up to 97 and 93%, respectively, and also to minimize the side reaction of the formation of ornithine-containing HD. For the arginine amide modified HD (5), we have also proposed an improved synthesis scheme. The ability of HD to cause the bacteria death in the composition of formed biofilms, including those consisting of resistant bacteria, was shown. After the effect of HDs on the biofilm at concentrations of 80 and 100 [Formula: see text]g/ml, the CFU decrease was 3–5/ml. The fluorescent microscopy confirmed the bacteria mortality in the biofilm. Electron microscopy showed structural damage (fragmentation) of the formed bacterial biofilm under the effect of HDs.

Study of the antibacterial properties of a composition based on chitosan obtained from dead bees Apis Mellifera

The article provides data on the development of a new thickening composition for printing cotton-lye fabric with antibacterial properties based on biodegradable polymers Chitosan synthesized from Apis Mellifera bee dead with CMC with addition of CMC and synthetic hydrolyzed acrylic emulsion. Studied the fungicidal properties of the developed mixed thickener for active dyes used in printing fabrics. As a result of observations, it was revealed that these new thickeners on the basis of exhibit pronounced antimicrobial activity in relation to the micelle fungus Aspergillus terreus. The optical density of the samples shows that these thickeners are resistant to mycelial fungi. Among thickeners, thickeners based on Uzhitan-?MS-HAE, Uzkhitan-CMS have the most pronounced bactericidal activity, and these thickeners are more stable, they can be used the next day and even on the second day for printing mixed fabrics.

Peculiarities of the course of acute radiation injury in mice against the background of iodine and selenium preparations

In experiments on mice the study of the radioprotective and radiotherapeutic efficacy of the combined use of the selenium-containing feed additive DAFS-25k and the iodine-containing preparation Monclavit-1 was carried out. It has been shown that intragastric administration of DAFS-25k oil solution 3 hours before the total, external, single exposure to γ-radiation, and the subsequent (in 12 hours) intragastric administration of an aqueous solution of Monclavit-1, increases the survival rate of irradiated animals to 67% versus 17% in the control animals. The mechanisms of radioprotective efficacy are assumed to be the antioxidant activity of selenium compounds in DAFS-25k, normalization of thyroid function and relief of gastrointestinal syndrome due to the pronounced antimicrobial activity of Monclavit-1.

Study of the antibacterial properties of a composition based on chitosan obtained from dead bees Apis Mellifera

The article provides data on the development of a new thickening composition for printing cotton-lye fabric with antibacterial properties based on biodegradable polymers Chitosan synthesized from Apis Mellifera bee dead with CMC with addition of CMC and synthetic hydrolyzed acrylic emulsion. Studied the fungicidal properties of the developed mixed thickener for active dyes used in printing fabrics. As a result of observations, it was revealed that these new thickeners on the basis of exhibit pronounced antimicrobial activity in relation to the micelle fungus Aspergillus terreus. The optical density of the samples shows that these thickeners are resistant to mycelial fungi. Among thickeners, thickeners based on Uzhitan-?MS-HAE, Uzkhitan-CMS have the most pronounced bactericidal activity, and these thickeners are more stable, they can be used the next day and even on the second day for printing mixed fabrics.

Evaluation of The Antioxidant, Antimicrobial, and Anticancer Activities of Dicliptera bupleuroides Isolated Compounds Using In Vitro and In Silico Studies.

Phytochemical investigation of chloroform fraction (DBC) and ethyl acetate fraction (DBE) of D. bupleuroides (Acanthaceae) resulted in the isolation of β-sitosterol (1) from DBC and vanillic acid (2) from DBE, which were first to be isolated from D. bupleuroides. β-Sitosterol (1) exhibited substantial antioxidant activity (IC50 = 198.87 µg/mL), whereas vanillic acid (2) showed significant antioxidant power (IC50 = 92.68 µg/mL) employing 1,1-diphenyl-2-picrylhydrazyl (DPPH*) radical scavenging capacity assay. Both compounds showed pronounced antimicrobial activity using the agar disc diffusion method, particularly against fungi showing MIC values of 0.182 and 0.02 concerning Candida albicans, respectively, and 0.001 mg/mL regarding Penicillium notatum. They revealed considerable antibacterial activity with MIC values ranging between 0.467 and 0.809 mg/mL. Vanillic acid (2) exhibited substantial anticancer potential displaying 48.67% cell viability at a concentration of 100 μg/mL using MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-Diphenyl-2H-Tetrazolium Bromide) assay concerning HepG2 cell lines. These results were further consolidated by in silico studies on different enzymes, where vanillic acid displayed a high fitting score in the active pockets of DNA-gyrase, dihydrofolate reductase, aminoglycoside nucleotidyltransferase, and β-lactamase. It also inhibited human cyclin-dependent kinase 2 (CDK-2) and DNA topoisomerase II, as revealed by the in silico studies. ADME/TOPKAT (absorption, distribution, metabolism, excretion, and toxicity) prediction showed that vanillic acid exhibited reasonable pharmacodynamic, pharmacokinetic, and toxicity properties and, thus, could perfectly together with D. bupleuroides crude extract be incorporated in pharmaceutical preparations to counteract cancer and microbial invasion, as well as oxidative stress. Thus, it is concluded that D. bupleroides could be a potential source of therapeutically active compounds, which would be helpful for the discovery of clinically effective and safe drugs.

Polyphenol rich extracts of Geranium L. species as potential natural antioxidant and antimicrobial agents.

Plants and plant extracts are of great scientific interest due to the chemical diversity and pharmacological properties of present bioactive molecules. The Geranium L. species are widely used in ethnomedicine. In the current study, the total phenolic and tannin content, antioxidant and antimicrobial activity of methanol extracts of eight Geranium species were investigated. The total phenolic and tannin content were determined by the FC method. Antioxidant capacity was evaluated in FRAP, DPPH, and biochemical assays, while antimicrobial activity was examined using the broth microdilution method. The high total phenolic (170.64-636.32 mg GAE/g dry extract) and tannin content (37.80-414.02 mg GAE/g DE), along with significant total antioxidant (FRAP values 1.13-8.80 mmol Fe2+/g) and DPPH radical scavenging activity (SC50 values 4.24-34.52 µg/mL) were observed. The prominent antioxidant capacity was confirmed in biochemical assays (OS values -1.47 - -13.02). The extracts exhibited significant antimicrobial activity against ATTC strains (MICs dominantly in the range of 12.5-200 µg/mL) as well as against clinical isolates of E. coli (MICs mostly 50 and 100 µg/mL). The pronounced antioxidant and antimicrobial activity can be due to the high phenolic content, particularly due to the presence of hydrolyzable tannins. Based on the high content of polyphenols, pronounced antioxidant and antimicrobial activities, the examined extracts are promising natural antioxidant and antimicrobial agents with the potential medicinal purpose and use as a functional food.

Bioactive Secondary Metabolites from Endophytic Aspergillus terreus AH1 Isolated from Ipomoea carnea Growing in Egypt

Growing evidence indicates that the endophytic fungus Aspergillus is one of rich sources of natural products with a broad spectrum of biological activities. In our effort to isolate and to identify biologically active metabolites from naturally occurring sources, two endophytic fungi have been isolated from the tissues of Ipomoea carnea. Among the two isolates, one fungus displayed pronounced antimicrobial activity, against pathogenic microbes include Gram+ve bacteria; Staphylococcus aureus and Bacillus subtilis, Gram–ve bacteria; Pseudomonas aeruginosa and Escherichia coli and Yeasts; Candida albicans with inhibition zone range from 16-19 mm. The most potent isolate has been identified genetically by sequencing of 18S rRNA gene as Aspergillus terreus AH1. Bio guided-fractionation and isolation of Aspergillus terreus AH1 extract led to identification of five compounds namely; (+)-asterrelenin (1), (±)-periplanamide B (2), butyrolactone I (3), pyranterrone D (4), and Arenarin A (5). The identified compounds showed a strong antibiofilm activity against human pathogenic bacteria such as Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli and Bacillus subtilis. Moreover, the compound ((±)-periplanamide B) has strong activity against some carcinoma cells such as HCT116, HePG 2 and MCF7

Physicochemical and nutritional profile of leaves, flowers, and fruits of the edible halophyte chorão-da-praia (Carpobrotus edulis) on Portuguese west shores

Leaves, flowers and fruits from the edible halophyte chorão-da-praia (Carpobrotus edulis), harvested in the Portuguese western sea shores, were characterized regarding their proximate composition, fatty acid profile, pigments, phenolic compounds, antioxidant and antimicrobial activities. Fruits had the highest amount of carbohydrates (70.2 ± 1.6%) and the lowest of protein (4.67 ± 0.22%) and ash (22.0 ± 1.0%) contents. No significant differences were observed in the lipid fraction. Leaves were mainly constituted by saturated (52.6 ± 1.3%) fatty acids (FA), whereas fruits showed the highest amount of polyunsaturated FA (48.6 ± 3.1%). Chlorophylls and carotenoids were more abundant in leaves. Aqueous-ethanolic (1:1, v/v) extract of flowers exhibited the highest phenolic content (299 ± 8 μg/mg of gallic acid equivalents), by the Folin–Ciocalteu methodology, as well as the strongest antioxidant activity (IC50 = 11.83 ± 1.0 μg/mL and 7.82 ± 0.24 μmol/mg of ascorbic acid equivalents by the DPPH and FRAP methods, respectively). Also, flowers extract showed the most pronounced antimicrobial activity by the microtiter broth dilution method. Mass and tandem mass spectra revealed that the most abundant species in all extracts were glycosylated and/or acetylated O-Methyl flavonols, mainly derived from syringetin and laricitrin. Nuclear magnetic resonance was also employed for complementary confirmation of the syringetin moieties. Regarding the profile in polyphenols, when comparing leaves, flowers and fruits, one concluded that there were clearly differences in the relative amount of these polyphenols, being flowers richer in the syringetin derivatives. In conclusion, this edible plant, classified as an invasive species of the Portuguese coast, highlights for its richness in bioactive compounds with potential application in the food industry.

ANTIMICROBIAL ACTIVITY OF WATER-ETHANOLIC EXTRACTIONS FROM QUERCUS ROBUR L. LEAVES AND BUDS

The problem of finding new antimicrobial drugs based on medicinal plant raw materials in modern pharmaceutical practice, is still relevant. There are interesting plant objects that have an antimicrobial action due to the content of a complex of biologically active substances in them. Quercus robur L. is a promising plant object, medicinal plant raw materials of which can be used for the development of new antimicrobial drugs. The aim of the study is screening of the antimicrobial activity of water-ethanolic extractions from Quercus robur L leaves and buds. Materials and methods. The determination of the minimum inhibitory concentration was carried out by the method of double serial dilutions in Mueller-Hinton nutrient broth (Bio-Rad, USA). As test cultures, strains of microorganisms of the American Type Culture Collection (ATCC) were used: Staphylococcus aureus (ATCC 29213), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), as well as Candida albicans (a clinical strain). The incubation was carried out at the temperature of 35°C for 24 hours. Simultaneously, an experiment was carried out to establish a "negative" control. The results were assessed visually by the presence / absence of the growth of microorganisms in test tubes with the corresponding dilutions of the test samples. Results. In the course of the study, it was found out that water-ethanolic extractions of Quercus robur L. leaves have the greatest antimicrobial effect against strains of Staphylococcus aureus and Escherichia coli . The water-ethanolic extractions of Quercus robur L. buds exhibit a pronounced antimicrobial activity against Pseudomonas aeruginosa and Candida albicans strains. It was revealed that the preparation of Quercus robur L. leaves tincture in the raw material:extractant ratio of 1:5 has a pronounced antimicrobial effect on the strains of Pseudomonas aeruginosa , Staphylococcus aureus , and with a higher multiplicity of dilution - on the strains of Escherichia coli and Candida albicans . The drug tincture of Quercus robur L. buds in the raw material:extractant ratio of 1:5 has a pronounced antimicrobial effect on the strains of microorganisms P. aeruginosa, S. aureus, E. coli and C. albicans in an eight-fold dilution. With respect to P. aeruginosa strains, antimicrobial activity was observed in 16-fold dilutions. The most pronounced antimicrobial effect was recorded against the C. albicans strain in a 32-fold dilution. As a result of the study, it can be concluded that to obtain the antimicrobial drugs - tincture of Quercus robur L. leaves and buds - is advisable to use the optimal extractant – 70% alcohol in a raw material:extractant ratio of 1:5. With these parameters of extraction, the greatest antimicrobial effect is observed in relation to the studied strains of the microorganisms. 70% alcohol has also a better penetrating ability into the deep layers of the epidermis in comparison with higher concentrations. Conclusion. The results of the screening analysis of the antimicrobial activity will be used as a justification for the introduction of antimicrobial drugs based on the leaves and buds of the Quercus robur L. in a medical and pharmaceutical practice.

Synthesis and antimicrobial activity of s-substituted derivatives of 1,2,4-triazol-3-thiol

The aim of the work. 1,2,4-triazole derivatives possess a wide range of pharmacological activity, so they are used for the development of drugs and active pharmaceutical ingredients. Due to the reactivity of 1,2,4-triazoles there are many options for their further structural modification on different reaction centers. Therefore, the aim of the work was to obtain new S-substituted derivatives of 1,2,4-triazole-3-thiols, study physicochemical parameters of the substances synthesized, evaluate the antimicrobial activity of new S-derivatives of the 4-R1-5-((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazole-3-thiol series, and study some regularities of the “structure – biological activity” relationship for the synthesized compounds as well.
 Materials and methods. The subject of the study was new S-substituted 1,2,4-triazoles containing 2-oxopropan-1-yl and 2-aryl-2-oxoethan-1-yl substituents. The antimicrobial activity was studied by double serial dilutions on test cultures of Staphylococcus aureus (ATCC 25923), Escherichia coli (ATCC 25922), Pseudomonas aeruginosa (ATCC 27853), and Candida albicans (ATCC 885-653).
 The results of the biological screening showed that at a concentration of 125 g/mL, all synthesized substances showed activity (MIC – in the range of 31.25 - 62.5 μg/mL, MBCK - in the range of 62.5–125 μg/mL) against strains of Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Candida albicans. Variation of substituents on the sulfur atom did not lead to a significant change in antimicrobial and antifungal activities among derivatives of 4-R1-5-((3-(pyridin-4-yl)-1H-1,2,4-triazole-5-yl) thio)methyl)-4H-1,2,4-triazole-3-thiols.
 Conclusions. Biological screening data indicate the prospects for the search for new antimicrobial substances among the abovementioned derivatives of 1,2,4-triazoles. The most active compounds were 1-((4-ethyl-5-((3-(pyridin-4-yl)-1H-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazol-3-yl)thio)propan-2-one and 1-(4-methoxyphenyl)-2-(4-ethyl-5-(((3-(pyridin-4-yl)-1H)-1,2,4-triazol-5-yl)thio)methyl)-4H-1,2,4-triazol-3-yl)thio)ethanone, which showed the most pronounced antimicrobial activity against the Pseudomonas aeruginosa strain (MIC – 31.25 μg/mL, MBcK - 62.5 μg/mL)

XYLOTROPHIC FUNGUS Trichoderma atroviride: CULTIVATION, EXTRACELLULAR HYDROLYTIC AND ANTIMICROBIAL ACTIVITY

Xylotrophic fungi are well known by their ability to excrete enzymes into environment. These fungi have important biotechnological potential and some of them produce industrial enzymes. Besides, xylotrophic fungal species have recently attracted a lot of attention among researchers as a source of antibacterial drugs. Aim. To analyze the effect of the carbon source in the culture medium, as well as the conditions of deep cultivation on the mycelium yield, proteolytic, cellulolytic and antimicrobial activity of the culture liquid of Trichoderma atroviride. Methods. Deep culture methods were used, partial purification was carried out with salting and subsequent dialysis, the cellulolytic activity was determined spectrophotometrically, antimicrobial activity was determined using the disc diffusion technique. Statistical analysis was performed using STATISTICA 6.0 software. Results. The highest cellulolytic activity (0.50±0.03 units/ml), mycelium yield and the smallest colony diameter were detected when cellulose was used as a carbon source. However, the highest proteolytic activity of the culture liquid was observed with glucose as a carbon source. The optimal temperature range for hydrolase activity was shown to be in the range of 25-30 °C. In comparison with Pleurotus ostreatus, the culture liquid of T. atroviride not only has more pronounced antimicrobial activity, but also inhibits the growth of Candida albicans. Conclusions. The culture liquid of isolated strain T. atroviride is a promising source of hydrolytic enzymes that can be used in organic farming and industry. The purified preparation obtained from the culture liquid of T. atroviride showed significant antimicrobial activity and can be successfully used for drug development in the future.

Study of the antimicrobial activity of the bark extracts of <i>Quercus robur</i> L.

The purpose of this study is to carry out comparative analysis of the antimicrobial activity of water-ethanolic and chloroform extractions from the bark of Quercus robur L.
 The determination of the minimum inhibitory concentration was carried out by the method of double serial dilutions in Mueller-Hinton nutrient broth (Bio-Rad, USA). Pseudomonas aeruginosa, Staphylococcus aureus, Escherichia coli, Candida albicans were used as test cultures.
 It was revealed that the greatest antimicrobial effect was exhibited by water-ethanolic extractions from Q. robur L. bark in ethanol concentrations of 60%, 70% and 96% ethanol in relation to strains of microorganisms P. aeruginosa and C. albicans. The lowest antimicrobial activity against strains of microorganisms E. coli and S. aureus was observed in 40% of water-ethanolic extractions. Chloroform extracts of Q. robur L. bark has a pronounced antimicrobial activity against C. albicans and P. aeruginosa strains. It is proposed to use 60% ethanol as the optimal concentration of ethanol for the bark of Q. robur L., since at the given concentration of ethanol, the maximum antimicrobial effect is observed, and the balance between the release of tannins and flavonoids into the dosage form also preserves.
 This study contributes to solving the issue of recycling wood waste of Q. robur L. and their rational use in pharmaceutical practice.
 The obtained results can be used in the future to create antimicrobial drugs based on the bark of Q. robur L.

The effect of long-term doxycycline treatment in a mouse model of cigarette smoke-induced emphysema and pulmonary hypertension.

Chronic obstructive pulmonary disease (COPD) is a major cause of death and a still incurable disease, comprising emphysema and chronic bronchitis. In addition to airflow limitation, patients with COPD can suffer from pulmonary hypertension (PH). Doxycycline, an antibiotic from the tetracycline family, in addition to its pronounced antimicrobial activity, acts as a matrix metalloproteinase (MMP) inhibitor and has anti-inflammatory properties. Furthermore, doxycycline treatment exhibited a beneficial effect in several preclinical cardiovascular disease models. In preclinical research, doxycycline is frequently employed for gene expression modulation in Tet-On/Tet-Off transgenic animal models. Therefore, it is crucial to know whether doxycycline treatment in Tet-On/Tet-Off systems has effects independent of gene expression modulation by such systems. Against this background, we assessed the possible curative effects of long-term doxycycline administration in a mouse model of chronic CS exposure. Animals were exposed to cigarette smoke (CS) for 8 mo and then subsequently treated with doxycycline for additional 3 mo in room air conditions. Doxycycline decreased the expression of MMPs and general pro-inflammatory markers in the lungs from CS-exposed mice. This downregulation was, however, insufficient to ameliorate CS-induced emphysema or PH. Tet-On/Tet-Off induction by doxycycline in such models is a feasible genetic approach to study curative effects at least in established CS-induced emphysema and PH. However, we report several parameters that are influenced by doxycycline and use of a Tet-On/Tet-Off system when evaluating those parameters should be interpreted with caution.

ОЦЕНКА КЛИНИЧЕСКОЙ ЭФФЕКТИВНОСТИ ЗУБНОЙ ПАСТЫ, СОДЕРЖАЩЕЙ ЭКСТРАКТ ГРЕЙПФРУТА И ЛИЗАТЫ LYSOTECH И PROTELYSE, В КОМПЛЕКСНОМ ЛЕЧЕНИИ ВОСПАЛИТЕЛЬНЫХ ЗАБОЛЕВАНИЙ ПАРОДОНТА

The preventive direction in dentistry is the leading one today. Individual oral hygiene plays a significant role in preventing the development of inflammatory periodontal diseases. The use of therapeutic and prophylactic toothpastes containing natural components with antibacterial properties is promising. Among plant extracts, grapefruit extract has the most pronounced antimicrobial activity. LysoTech and ProteLyse lysates, which have antimicrobial and immunomodulatory effects, have long been used in dentistry in the form of tablets for resorption in the complex treatment of various diseases. Their introduction into toothpastes is also considered a promising direction for the prevention and treatment of oral pathology. The aim of our study was to clinically evaluate the effectiveness of therapeutic and prophylactic toothpaste, which contains grapefruit extract and LysoTech and ProteLyse lysates, in patients with inflammatory diseases of periodontal tissues. A clinical and laboratory comparative study of two therapeutic and prophylactic toothpastes was conducted. The composition of the samples was identical, except for two components: grapefruit extract and LysoTech and ProteLyse lysates. The study involved 60 volunteers who were divided into two groups depending on the toothpastes used. The purifying and anti-inflammatory effects of the samples were evaluated for one month. An in vitro laboratory study was also conducted to identify the antimicrobial properties of toothpastes. During the work, high clinical results were noted in a group of volunteers using toothpaste with grapefruit seed extract and bacterial lysates, which are expressed in a decrease in PMA and SBI indices, and an improvement in oral hygiene. According to a laboratory study, the toothpaste containing grapefruit extract and LysoTech and ProteLyse lysates has a more pronounced antimicrobial and antifungal effect, which indicates a high preventive and therapeutic potential of the test sample.

Synthesis, biological evaluation and molecular docking studies of novel quinazolinones as antitubercular and antimicrobial agents

In the present study, a series of novel quinazolinone hybrids, viz. triazepino-quinazolinones 4, thiazolo-triazolo-quinazolinones 7 and triazolo-quinazolinones 8 have been synthesized from the key intermediate 3-(substituted phenyl)-2-hydrazinoquinazolin-4(3H)-ones 3. All the newly synthesized compounds were characterized by means of spectral (IR, 1H NMR, 13C NMR) and elemental analysis. The target compounds were biologically screened for their in vitro antimicrobial and antitubercular activities against pathogenic strain. The results of bioassay demonstrated that some of the compounds exhibited pronounced antimicrobial activity comparable to that of standard drugs tested under similar conditions. Compounds 4c, 4e, 7e and 8b showed relatively very good inhibitory activity against pathogenic bacteria with minimum inhibitory concentration (MIC) of 2.6 μg/mL, 5.2 μg/mL, while the rest of the compounds showed moderate activity. Compounds 4c and 8b were found to be nearly equipotent with ciprofloxacin against P. aeruginosa with MIC 5.2 μg/mL, while compound 8b was more potent against pathogenic bacteria S. aureus. It is very remarkable that four compounds, 4c, 4e, 7e and 8b showed pronounced antifungal activity against selected pathogenic fungi, A. niger, C. albicans with MIC 2.6 μg/mL and 5.2 μg/mL. The antitubercular activity of synthesized compounds reveal that compound 8b showed better activity than the other compounds with a MIC of 5.2 μg/mL against M. tuberculosis (H37Rv). Molecular docking studies of the compounds were performed to rationalize the inhibitory properties of these compounds and results showed that these compounds have good binding energy and better binding affinity within the active pocket, thus these compounds may be considered as potent inhibitors towards selective targets.

In vitro antibacterial and antioxidant activity of Rosmarinus officinalis

Rosmarinus officinalis L. is known for its antioxidant and antibacterial properties against a variety of microorganisms. In this work, research has been carried out on pharmacy rosemary. Its antioxidant and antimicrobial properties have been determined. This study showed that the ethanol extract of R. officinalis L. has a pronounced antimicrobial activity against strains of both gram-positive and gram-negative bacteria. The extract also showed good antioxidant activity. Rosemary showed significantly more potent antibacterial activity against E. coli. The diameter of the zone of oppression was 17 mm. Thus, Rosemary Pharmaceutical has demonstrated potential as a dietary supplement due to its stronger antibacterial activity.