Analysis of the Model of Atherosclerosis Formation in Pig Hearts as a Result of Impaired Activity of DNA Repair Enzymes.

Excessive consumption of food rich in saturated fatty acids and carbohydrates can lead to metabolic disturbances and cardiovascular disease. Hyperlipidemia is a significant risk factor for acute cardiac events due to its association with oxidative stress. This leads to arterial wall remodeling, including an increase in the thickness of the intima media complex (IMT), and endothelial dysfunction leading to plaque formation. The decreased nitric oxide synthesis and accumulation of lipids in the wall result in a reduction in the vasodilating potential of the vessel. This study aimed to establish a clear relationship between markers of endothelial dysfunction and the activity of repair enzymes in cardiac tissue from a pig model of early atherosclerosis. The study was conducted on 28 female Polish Landrace pigs, weighing 40 kg (approximately 3.5 months old), which were divided into three groups. The control group (n = 11) was fed a standard, commercial, balanced diet (BDG) for 12 months. The second group (n = 9) was fed an unbalanced, high-calorie Western-type diet (UDG). The third group (n = 8) was fed a Western-type diet for nine months and then switched to a standard, balanced diet (regression group, RG). Control examinations, including blood and urine sampling, were conducted every three months under identical conditions with food restriction for 12 h and water restriction for four hours before general anesthesia. The study analyzed markers of oxidative stress formed during lipid peroxidation processes, including etheno DNA adducts, ADMA, and NEFA. These markers play a crucial role in reactive oxygen species analysis in ischemia-reperfusion and atherosclerosis in mammalian tissue. Essential genes involved in oxidative-stress-induced DNA demethylation like OGG1 (8-oxoguanine DNA glycosylase), MPG (N-Methylpurine DNA Glycosylase), TDG (Thymine-DNA glycosylase), APEX (apurinic/apirymidinic endodeoxyribonuclease 1), PTGS2 (prostaglandin-endoperoxide synthase 2), and ALOX (Arachidonate Lipoxygenase) were measured using the Real-Time RT-PCR method. The data suggest that high oxidative stress, as indicated by TBARS levels, is associated with high levels of DNA repair enzymes and depends on the expression of genes involved in the repair pathway. In all analyzed groups of heart tissue homogenates, the highest enzyme activity and gene expression values were observed for the OGG1 protein recognizing the modified 8oxoG. Conclusion: With the long-term use of an unbalanced diet, the levels of all DNA repair genes are increased, especially (significantly) Apex, Alox, and Ptgs, which strongly supports the hypothesis that an unbalanced diet induces oxidative stress that deregulates DNA repair mechanisms and may contribute to genome instability and tissue damage.

Evaluation of Antibacterial Activity against Nosocomial Pathogens of an Enzymatically Derived α-Aminophosphonates Possessing Coumarin Scaffold.

The purpose of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and α-amino dimethyl phosphonate moieties, on antimicrobial activity against selected strains of multidrug-resistant nosocomial pathogenic bacteria. The previously developed enzyme-catalysed Kabachnik-Fields protocol allowed us to obtain the studied compounds with high yields which were free from metal impurities. The structure-activity relationship revealed that inhibitory activity is strongly related to the presence of the trifluoromethyl group (CF3-) in the coumarin scaffold. MIC and MBC studies carried out on six selected pathogenic bacterial strains (Gram-positive pathogenic Staphylococcus aureus (ATCC 23235) strain, as well as on Gram-negative Acinetobacter baumannii (ATCC 17978), Pseudomonas aeruginosa (ATCC 15442), Enterobacter cloacae (ATCC 49141), Porphyromonas gingivalis (ATCC 33277), and Treponema denticola (ATCC 35405)) have shown that tested compounds show a strong bactericidal effect at low concentrations. Among all agents investigated, five exhibit higher antimicrobial activity than those observed for commonly used antibiotics. It should be noted that all the compounds tested showed very high activity against S. aureus, which is the main source of nosocomial infections that cause numerous fatalities. Furthermore, we have shown that the studied coumarin-based α-aminophosphonates, depending on their structural characteristics, are non-selective and act efficiently against various Gram-positive and Gram-negative pathogens, which is of great importance for hospitalised patients.

Biocontrol of fungal phytopathogens by Bacillus pumilus.

Plant growth-promoting bacteria are one of the most interesting methods of controlling fungal phytopathogens. These bacteria can participate in biocontrol via a variety of mechanisms including lipopeptide production, hydrolytic enzymes (e.g., chitinase, cellulases, glucanase) production, microbial volatile organic compounds (mVOCs) production, and induced systemic resistance (ISR) triggering. Among the bacterial genera most frequently studied in this aspect are Bacillus spp. including Bacillus pumilus. Due to the range of biocontrol traits, B. pumilus is one of the most interesting members of Bacillus spp. that can be used in the biocontrol of fungal phytopathogens. So far, a number of B. pumilus strains that exhibit biocontrol properties against fungal phytopathogens have been described, e.g., B. pumilus HR10, PTB180, B. pumilus SS-10.7, B. pumilus MCB-7, B. pumilus INR7, B. pumilus SE52, SE34, SE49, B. pumilus RST25, B. pumilus JK-SX001, and B. pumilus KUDC1732. B. pumilus strains are capable of suppressing phytopathogens such as Arthrobotrys conoides, Fusarium solani, Fusarium oxysporum, Sclerotinia sclerotiorum, Rhizoctonia solani, and Fagopyrum esculentum. Importantly, B. pumilus can promote plant growth regardless of whether it alters the native microbiota or not. However, in order to increase its efficacy, research is still needed to clarify the relationship between the native microbiota and B. pumilus. Despite that, it can already be concluded that B. pumilus strains are good candidates to be environmentally friendly and commercially effective biocontrol agents.

Molecular Oxygen Levels and Percentages of DNA Damage in TPN Patients.

Total parenteral nutrition (TPN) is a life-saving therapy for patients with intestinal failure, but it carries the risk of complications, including an increase in liver enzymes alanine aminotransferase (ALT) and aspartate aminotransferase (AST) after long-term use. Patients receiving chronic TPN are also exposed to metabolic stress from both the underlying disease and parenteral nutrition. The aim of this study was to compare the concentration of liver transaminases AST and ALT in relation to the rate of oxygen consumption in platelet mitochondria in patients receiving long-term TPN with the degree of oxidative stress induced by lipid emulsions, and to explain their role in cellular energy metabolism and changes in the liver based on the percentage of genomic DNA damage. The study group consisted of 86 TPN patients, while the control group consisted of 86 healthy volunteers who were fed only orally. The results of the study showed that the percentage of molecular oxygen depended on the type of lipid emulsion supplied. Analyzing time on TPN as a factor, we observed a decrease in percentage genomic DNA damage and an increase in percentage molecular oxygen in cells. It remains unclear whether TPN has a direct effect on genomic DNA damage and the level of molecular oxygen in cells during the course of treatment. In conclusion, this study provides important insights into the potential effects of TPN on liver enzymes and cellular metabolism. Further research is needed to better understand the underlying mechanisms and to develop strategies to minimize the risk of complications associated with TPN.

Evaluation of Antimicrobial Activities against Various E. coli Strains of a Novel Hybrid Peptide-LENART01.

Finding the ideal antimicrobial drug with improved efficacy and a safety profile that eliminates antibiotic resistance caused by pathogens remains a difficult task. Indeed, there is an urgent need for innovation in the design and development of a microbial inhibitor. Given that many promising antimicrobial peptides with excellent broad-spectrum antibacterial properties are secreted by some frog species (e.g., bombesins, opioids, temporins, etc.), our goal was to identify the antimicrobial properties of amphibian-derived dermorphin and ranatensin peptides, which were combined to produce a hybrid compound. This new chimera (named LENART01) was tested for its antimicrobial activity against E. coli strains K12 and R1-R4, which are characterized by differences in lipopolysaccharide (LPS) core oligosaccharide structure. The results showed that LENART01 had superior activity against the R2 and R4 strains compared with the effects of the clinically available antibiotics ciprofloxacin or bleomycin (MIC values). Importantly, the inhibitory effect was not concentration dependent; however, LENART01 showed a time- and dose-dependent hemolytic effect in hemolytic assays.

Plant Growth Promotion Using Bacillus cereus.

Plant growth-promoting bacteria (PGPB) appear to be a sensible competitor to conventional fertilization, including mineral fertilizers and chemical plant protection products. Undoubtedly, one of the most interesting bacteria exhibiting plant-stimulating traits is, more widely known as a pathogen, Bacillus cereus. To date, several environmentally safe strains of B. cereus have been isolated and described, including B. cereus WSE01, MEN8, YL6, SA1, ALT1, ERBP, GGBSTD1, AK1, AR156, C1L, and T4S. These strains have been studied under growth chamber, greenhouse, and field conditions and have shown many significant traits, including indole-3-acetic acid (IAA) and aminocyclopropane-1-carboxylic acid (ACC) deaminase production or phosphate solubilization, which allows direct plant growth promotion. It includes an increase in biometrics traits, chemical element content (e.g., N, P, and K), and biologically active substances content or activity, e.g., antioxidant enzymes and total soluble sugar. Hence, B. cereus has supported the growth of plant species such as soybean, maize, rice, and wheat. Importantly, some B. cereus strains can also promote plant growth under abiotic stresses, including drought, salinity, and heavy metal pollution. In addition, B. cereus strains produced extracellular enzymes and antibiotic lipopeptides or triggered induced systemic resistance, which allows indirect stimulation of plant growth. As far as biocontrol is concerned, these PGPB can suppress the development of agriculturally important phytopathogens, including bacterial phytopathogens (e.g., Pseudomonas syringae, Pectobacterium carotovorum, and Ralstonia solanacearum), fungal phytopathogens (e.g., Fusarium oxysporum, Botrytis cinerea, and Rhizoctonia solani), and other phytopathogenic organisms (e.g., Meloidogyne incognita (Nematoda) and Plasmodiophora brassicae (Protozoa)). In conclusion, it should be noted that there are still few studies on the effectiveness of B. cereus under field conditions, particularly, there is a lack of comprehensive analyses comparing the PGP effects of B. cereus and mineral fertilizers, which should be reduced in favor of decreasing the use of mineral fertilizers. It is also worth mentioning that there are still very few studies on the impact of B. cereus on the indigenous microbiota and its persistence after application to soil. Further studies would help to understand the interactions between B. cereus and indigenous microbiota, subsequently contributing to increasing its effectiveness in promoting plant growth.

Enzymatic Synthesis of a Novel Coumarin Aminophosphonates: Antibacterial Effects and Oxidative Stress Modulation on Selected E. coli Strains.

The objective of the present study was to evaluate the synergistic effect of two important pharmacophores, coumarin and α-amino dimethyl phosphonate moieties, on antimicrobial activity toward selected LPS-varied E. coli strains. Studied antimicrobial agents were prepared via a Kabachnik-Fields reaction promoted by lipases. The products were provided with an excellent yield (up to 92%) under mild, solvent- and metal-free conditions. A preliminary exploration of coumarin α-amino dimethyl phosphonate analogs as novel antimicrobial agents was carried out to determine the basic features of the structure responsible for the observed biological activity. The structure-activity relationship revealed that an inhibitory activity of the synthesized compounds is strongly related to the type of the substituents located in the phenyl ring. The collected data demonstrated that coumarin-based α-aminophosphonates can be potential antimicrobial drug candidates, which is particularly crucial due to the constantly increasing resistance of bacteria to commonly used antibiotics.

Bioremediation of Heavy Metals by the Genus Bacillus.

Environmental contamination with heavy metals is one of the major problems caused by human activity. Bioremediation is an effective and eco-friendly approach that can reduce heavy metal contamination in the environment. Bioremediation agents include bacteria of the genus Bacillus, among others. The best-described species in terms of the bioremediation potential of Bacillus spp. Are B. subtilis, B. cereus, or B. thuringiensis. This bacterial genus has several bioremediation strategies, including biosorption, extracellular polymeric substance (EPS)-mediated biosorption, bioaccumulation, or bioprecipitation. Due to the above-mentioned strategies, Bacillus spp. strains can reduce the amounts of metals such as lead, cadmium, mercury, chromium, arsenic or nickel in the environment. Moreover, strains of the genus Bacillus can also assist phytoremediation by stimulating plant growth and bioaccumulation of heavy metals in the soil. Therefore, Bacillus spp. is one of the best sustainable solutions for reducing heavy metals from various environments, especially soil.

Aluminium(III) Oxide-The Silent Killer of Bacteria.

In this article, we describe the antimicrobial properties of pristine anodised aluminium oxide matrices-the material many consider biologically inert. During a typical anodisation process, chromium and chlorine compounds are used for electropolishing and the removal of the first-step aluminium oxide. Matrices without the use of those harmful compounds were also fabricated and tested for comparison. The antibacterial tests were conducted on four strains of Escherichia coli: K12, R2, R3 and R4. The properties of the matrices were also compared to the three types of antibiotics: ciprofloxacin, bleomycin and cloxacillin using the Minimal Inhibitory Concentration (MIC) and Minimum Bactericidal Concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than the aforementioned antibiotics. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA.

Synthesis and Antimicrobial Activity of the Pathogenic E. coli Strains of p-Quinols: Additive Effects of Copper-Catalyzed Addition of Aryl Boronic Acid to Benzoquinones.

A mild and efficient protocol for the synthesis of p-quinols under aqueous conditions was developed. The pivotal role of additives in the copper-catalyzed addition of aryl boronic and heteroaryl boronic acids to benzoquinones was observed. It was found that polyvinylpyrrolidone (PVP) was the most efficient additive used for the studied reaction. The noteworthy advantages of this procedure include its broad substrate scope, high yields up to 91%, atom economy, and usage of readily available starting materials. Another benefit of this method is the reusability of the catalytic system up to four times. Further, the obtained p-quinols were characterized on the basis of their antimicrobial activities against E. coli. Antimicrobial activity was further compared with the corresponding 4-benzoquinones and 4-hydroquinones. Among tested compounds, seven derivatives showed an antimicrobial activity profile similar to that observed for commonly used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained p-quinols constitute a suitable platform for further modifications, allowing for a convenient change in their biological activity profile.

A Series of Green Oxovanadium(IV) Precatalysts with O, N and S Donor Ligands in a Sustainable Olefins Oligomerization Process.

Designing catalyst systems based on transition metal ions and activators using the principles of green chemistry is a fundamental research goal of scientists due to the reduction of poisonous solvents, metal salts and organic ligands released into the environment. Urgent measures to reduce climate change are in line with the goals of sustainable development and the new restrictive laws ordained by the European Union. In this report, we attempted to use known oxovanadium(IV) green complex compounds with O, N and S donor ligands, i.e., [VO(TDA)phen] • 1.5 H2O (TDA = thiodiacetate), (phen = 1,10-phenanthroline), oxovanadium(IV) microclusters with 2-phenylpyridine (oxovanadium(IV) cage), [VOO(dipic)(2-phepyH)] • H2O (dipic = pyridine-2,6-dicarboxylate anion), (2-phepyH = 2-phenylpyridine), [VO(dipic)(dmbipy)] • 2H2O (dmbipy = 4,4'-dimethoxy-2,2'-dipyridyl) and [VO(ODA)(bipy)] • 2 H2O (ODA = oxydiacetate), (bipy = 2,2'-bipyridine), as precatalysts in oligomerization reactions of 3-buten-2-ol, 2-propen-1-ol, 2-chloro-2-propen-1-ol and 2,3-dibromo-2-propen-1-ol. The precatalysts, in most cases, turned out to be highly active because the catalytic activity exceeded 1000 g mmol-1·h-1. In addition, the oligomers were characterized by Fourier-transform infrared spectroscopy (FTIR), matrix-assisted laser desorption/ionization (MALDI-TOF-MS), thermogravimetric analysis (TGA) and differential scanning calorimetry (DSC) techniques.

The Synthesis and Evaluation of Diethyl Benzylphosphonates as Potential Antimicrobial Agents.

The impact of substituent at phenyl ring of diethyl benzylphosphonate derivatives on cytotoxic activity was studied. The organophosphonates were obtained based on developed palladium-catalyzed α, ß-homodiarylation of vinyl esters protocol. The new synthetic pathway toward 1,2-bis(4-((diethoxyphosphoryl)methyl)phenyl)ethyl acetate was proposed which significantly improves the overall yield of the final product (from 1% to 38%). Several newly synthesized organophosphonates were tested as new potential antimicrobial drugs on model Escherichia coli bacterial strains (K12 and R2-R3). All tested compounds show the highest selectivity and activity against K12 and R2 strains. Preliminary cellular studies using MIC and MBC tests and digestion of Fpg after modification of bacterial DNA suggest that selected benzylphosphonate derivatives may have greater potential as antibacterial agents than typically used antibiotics such as ciprofloxacin, bleomycin and cloxacillin. These compounds are highly specific for pathogenic E. coli strains based on the model strains used and may be engaged in the future as new substitutes for commonly used antibiotics, which is especially important due to the increasing resistance of bacteria to various drugs and antibiotics.

Functionalised Anodised Aluminium Oxide as a Biocidal Agent.

In this article, we describe the antimicrobial properties of a new composite based on anodic aluminium oxide (AAO) membranes containing propyl-copper-phosphonate units arranged at a predetermined density inside the AAO channels. The samples were prepared with four concentrations of copper ions and tested as antimicrobial drug on four different strains of Escherichia coli (K12, R2, R3 and R4). For comparison, the same strains were tested with three types of antibiotics using the minimal inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. Moreover, DNA was isolated from the analysed bacteria which was additionally digested with formamidopyrimidine-DNA glycosylase (Fpg) protein from the group of repair glycosases. These enzymes are markers of modified oxidised bases in nucleic acids produced during oxidative stress in cells. Preliminary cellular studies, MIC and MBC tests and digestion with Fpg protein after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than antibiotics such as ciprofloxacin, bleomycin and cloxacillin. The described composites are highly specific for the analysed model Escherichia coli strains and may be used in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the progressing pandemic era. The results show much stronger antibacterial properties of the functionalised membranes on the action of bacterial membranes in comparison to the antibiotics in the Fpg digestion experiment. This is most likely due to the strong induction of oxidative stress in the cell through the breakdown of the analysed bacterial DNA. We have also observed that the intermolecular distances between the functional units play an important role for the antimicrobial properties of the used material. Hence, we utilised the idea of the 2D solvent to tailor them.

Promiscuous Lipase-Catalyzed Knoevenagel-Phospha-Michael Reaction for the Synthesis of Antimicrobial ß-Phosphono Malonates.

An enzymatic route for phosphorous-carbon bond formation was developed by discovering new promiscuous activity of lipase. We reported a new metal-free biocatalytic method for the synthesis of pharmacologically relevant ß-phosphonomalononitriles via a lipase-catalyzed one-pot Knoevenagel-phospha-Michael reaction. We carefully analyzed the best conditions for the given reaction: the type of enzyme, temperature, and type of solvent. A series of target compounds was synthesized, with yields ranging from 43% to 93% by enzymatic reaction with Candida cylindracea (CcL) lipase as recyclable and, a few times, reusable catalyst. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The applicability of the same catalyst in the synthesis of ß-phosphononitriles is also described. Further, the obtained compounds were validated as new potential antimicrobial agents with characteristic E. coli bacterial strains. The pivotal role of such a group of phosphonate derivatives on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics. The impact of the ß-phosphono malonate chemical structure on antimicrobial activity was demonstrated. The crucial role of the substituents attached to the aromatic ring on the inhibitory action against selected pathogenic E. coli strains was revealed. Among tested compounds, four ß-phosphonate derivatives showed an antimicrobial activity profile similar to that obtained with currently used antibiotics such as ciprofloxacin, bleomycin, and cloxacillin. In addition, the obtained compounds constitute a convenient platform for further chemical functionalization, allowing for a convenient change in their biological activity profile. It should also be noted that the cost of the compounds obtained is low, which may be an attractive alternative to the currently used antimicrobial agents. The observed results are especially important because of the increasing resistance of bacteria to various drugs and antibiotics.

Influence of Open Chain and Cyclic Structure of Peptidomimetics on Antibacterial Activity in E. coli Strains.

An efficient method for the synthesis of functionalized peptidomimetics via multicomponent Ugi reaction has been developed. The application of trifluoroethanol (TFE) as a reaction medium provided desired products with good yields. Further, using the developed cyclisation reaction, the obtained peptidomimetics were transformed into the cyclic analogues (diketopiperazines, DKPs). The goal of the performed studies was to revised and compare whether the structure of the obtained structurally flexible acyclic peptidomimetics and their rigid cycling analogue DKPs affect antimicrobial activity. We studied the potential of synthesized peptidomimetics, both cyclic and acyclic, as antimicrobial drugs on model E. coli bacteria strains (k12, R2-R4). The biological assays reveal that DKPs hold more potential as antimicrobial drugs compared to open chain Ugi peptidomimetics. We believe that it can be due to the rigid cyclic structure of DKPs which promotes the membrane penetration in the cell of studied pathogens. The obtained data clearly indicate the high antibiotic potential of synthesized diketopiperazine derivatives over tested antibiotics.

Relationship between Structure and Antibacterial Activity of α-Aminophosphonate Derivatives Obtained via Lipase-Catalyzed Kabachnik-Fields Reaction.

We reported a new method dealing with the synthesis of novel pharmacologically relevant α-aminophosphonate derivatives via a lipase-catalyzed Kabachnik−Fields reaction with yields of up to 93%. The advantages of this protocol are excellent yields, mild reaction conditions, low costs, and sustainability. The developed protocol is applicable to a range of H-phosphites and organic amines, providing a wide substrate scope. A new class of α-aminophosphonate analogues possessing P-chiral centers was also synthesized. The synthesized compounds were characterized on the basis of their antimicrobial activities against E. coli. The impact of the various alkoxy groups on antimicrobial activity was demonstrated. The crucial role of the substituents, located at the aromatic rings in the phenylethyloxy and benzyloxy groups, on the inhibitory action against selected pathogenic E. coli strains was revealed. The observed results are especially important because of increasing resistance of bacteria to various drugs and antibiotics.

The Lactoferrin Phenomenon-A Miracle Molecule.

Numerous harmful factors that affect the human body from birth to old age cause many disturbances, e.g., in the structure of the genome, inducing cell apoptosis and their degeneration, which leads to the development of many diseases, including cancer. Among the factors leading to pathological processes, microbes, viruses, gene dysregulation and immune system disorders have been described. The function of a protective agent may be played by lactoferrin as a "miracle molecule", an endogenous protein with a number of favorable antimicrobial, antiviral, antioxidant, immunostimulatory and binding DNA properties. The purpose of this article is to present the broad spectrum of properties and the role that lactoferrin plays in protecting human cells at all stages of life.

Lactoferrin as a Human Genome "Guardian"-An Overall Point of View.

Structural abnormalities causing DNA modifications of the ethene and propanoadducts can lead to mutations and permanent damage to human genetic material. Such changes may cause premature aging and cell degeneration and death as well as severe impairment of tissue and organ function. This may lead to the development of various diseases, including cancer. In response to a damage, cells have developed defense mechanisms aimed at preventing disease and repairing damaged genetic material or diverting it into apoptosis. All of the mechanisms described above are part of the repertoire of action of Lactoferrin-an endogenous protein that contains iron in its structure, which gives it numerous antibacterial, antiviral, antifungal and anticancer properties. The aim of the article is to synthetically present the new and innovative role of lactoferrin in the protection of human genetic material against internal and external damage, described by the modulation mechanisms of the cell cycle at all its levels and the mechanisms of its repair.

Promiscuous Lipase-Catalyzed Markovnikov Addition of H-Phosphites to Vinyl Esters for the Synthesis of Cytotoxic α-Acyloxy Phosphonate Derivatives.

An enzymatic route for phosphorous-carbon- bond formation is developed by discovering new promiscuous activity of lipase. This biocatalytic transformation of phosphorous-carbon- bond addition leads to biologically and pharmacologically relevant α-acyloxy phosphonates with methyl group in α-position. A series of target compounds were synthesized with yields ranging from 54% to 83% by enzymatic reaction with Candida cylindracea (CcL) lipase via Markovnikov addition of H-phosphites to vinyl esters. We carefully analyzed the best conditions for the given reaction such as the type of enzyme, temperature, and type of solvent. The developed protocol is applicable to a range of H-phosphites and vinyl esters significantly simplifying the preparation of synthetically challenging α-pivaloyloxy phosphonates. Further, the obtained compounds were validated as new potential antimicrobial drugs with characteristic E. coli bacterial strains and DNA modification recognized by the Fpg protein, N-methyl purine glycosylases as new substrates. The impact of the methyl group located in the α-position of the studied α-acyloxy phosphonates on the antimicrobial activity was demonstrated. The pivotal role of this group on inhibitory activity against selected pathogenic E. coli strains was revealed. The observed results are especially important in the case of the increasing resistance of bacteria to various drugs and antibiotics.

The Evaluation of DHPMs as Biotoxic Agents on Pathogen Bacterial Membranes.

Herein, we present biological studies on 3,4-dihydropyrimidin-2(1H)-ones (DHPMs) obtained via Biginelli reaction catalyzed by NH4Cl under solvent-free conditions. Until now, DHPMs have not been tested for biological activity against pathogenic E. coli strains. We tested 16 newly synthesized DHPMs as antimicrobial agents on model E. coli strains (K12 and R2-R4). Preliminary cellular studies using MIC and MBC tests and digestion of Fpg after modification of bacterial DNA suggest that these compounds may have greater potential as antibacterial agents than typically used antibiotics, such as ciprofloxacin (ci), bleomycin (b) and cloxacillin (cl). The described compounds are highly specific for pathogenic E. coli strains based on the model strains used and may be engaged in the future as new substitutes for commonly used antibiotics in clinical and nosocomial infections in the pandemic era.