Antibacterial Design Research Articles

New piperazine and morpholine derivatives: Mass spectrometry characterization and evaluation of their antimicrobial activity

Recently, pharmaceutical research has been focused on the design of new antibacterial drugs with higher selectivity towards several strains. Major issues concern the possibility to obtain compounds with fewer side effects, at the same time effectively overcoming the problem of antimicrobial resistance. Several solutions include the synthesis of new pharmacophores starting from piperazine or morpholine core units. Mass spectrometry-based techniques offer important support for the structural characterization of newly synthesized compounds to design safer and more effective drugs for various medical conditions. Here, two new piperazine derivatives and four new morpholine derivatives were synthesized and structurally characterized through a combined approach of Fourier transform-ion cyclotron resonance (FT-ICR) and Linear Trap Quadrupole (LTQ) mass spectrometry. The support of both high-resolution and low-resolution mass spectrometric data namely accurate mass measurements, isotopic distribution and MSn spectra, was crucial to confirm the success of the synthesis. These compounds were further evaluated for inhibitory activity against a total of twenty-nine Gram-positive and Gram-negative bacteria to determine the action spectrum and the antimicrobial effectiveness. Results demonstrated compounds’ antimicrobial activity against many tested bacterial species, providing an inhibitory effect linked to different chemical structure and suggesting that the new-synthesized derivatives could be considered as promising antimicrobial agents.

Solution NMR chemical shift assignment of apo and molybdate-bound ModA at two pHs.

ModA is a soluble periplasmic molybdate-binding protein found in most gram-negative bacteria. It is part of the ABC transporter complex ModABC that moves molybdenum into the cytoplasm, to be used by enzymes that carry out various redox reactions. Since there is no clear analog for ModA in humans, this protein could be a good target for antibacterial drug design. Backbone 1H, 13C and 15N chemical shifts of apo and molybdate-bound ModA from E. coli were assigned at pHs 6.0 and 4.5. In addition, side chain atoms were assigned for apo ModA at pH 6.0. When comparing apo and molybdate-bound ModA at pH 6.0, large chemical shift perturbations are observed, not only in areas near the bound metal, but also in regions that are distant from the metal-binding site. Given the significant conformational change between apo and holo ModA, we might expect the large chemical shift changes to be more widespread; however, since they are limited to specific regions, the residues with large perturbations may reveal allosteric sites that could ultimately be important for the design of antibiotics that target ModA.

Phase separation of extracellular polymeric substances induced by bacteria responsive Nano-Antibiotics for drug-resistant bacterial infection management

Bacterial quorum sensing (QS) and bacterial extracellular polymeric substances (EPS) are the major challenges in treating biofilm chronic infection. Herein, we proposed targeting intervention phase separation of EPS by nano-antibiotics (Ir(ppy)2dmb-PAZ-HA) as an effective strategy for combating bacterial biofilm infection, in which Iridium complex (Ir(ppy)2dmb-CHO) and antibiotic (Pazufloxacin, PAZ) for synergistic antibacterial, and hyaluronic acid (HA) was used to enhance Ir(ppy)2dmb-PAZ release on-demand in biofilm microenvironment. In vitro results showed that Ir(ppy)2dmb-PAZ-HA holds excellent antibacterial activity and antibiofilm capacity. Importantly, Ir(ppy)2dmb-PAZ-HA can be target to regulate phase separation of EPS, and then interfere with biofilm formation, which is a competitive mechanism between Ir(ppy)2dmb-PAZ-HA and Methicillin-resistant Staphylococcus aureus (MRSA) itself. In addition, in vivo results confirmed that Ir(ppy)2dmb-PAZ-HA was able to accelerate biofilm chronic wound healing, and effectively alleviate bacterial acute lung infection. Accordingly, this study provides a new antibiofilm target, and provides a novel idea for the design of small molecular metal antibacterial drugs and antibiotic reuse.

The Molecular Basis of Catalysis by SDR Family Members Ketoacyl-ACP Reductase FabG and Enoyl-ACP Reductase FabI in Type-II Fatty Acid Biosynthesis.

The short-chain dehydrogenase/reductase (SDR) superfamily members acyl-ACP reductases FabG and FabI are indispensable core enzymatic modules and catalytic orientation controllers in type-II fatty acid biosynthesis. Herein, we report their distinct substrate allosteric recognition and enantioselective reduction mechanisms. FabG achieves allosteric regulation of ACP and NADPH through ACP binding across two adjacent FabG monomers, while FabI follows an irreversible compulsory order of substrate binding in that NADH binding must precede that of ACP on a discrete FabI monomer. Moreover, FabG and FabI utilize a backdoor residue Phe187 or a "rheostat" α8 helix for acyl chain length selection, and their corresponding triad residues Ser142 or Tyr145 recognize the keto- or enoyl-acyl substrates, respectively, facilitating initiation of nucleophilic attack by NAD(P)H. The other two triad residues (Tyr and Lys) mediate subsequent proton transfer and (R)-3-hydroxyacyl- or saturated acyl-ACP production.

Copper-Based Antibiotic Strategies: Exploring Applications in the Hospital Setting and the Targeting of Cu Regulatory Pathways and Current Drug Design Trends.

Classical antibacterial drugs were designed to target specific bacterial properties distinct from host human cells to maximize potency and selectivity. These designs were quite effective as they could be easily derivatized to bear next-generation drugs. However, the rapid mutation of bacteria and their associated acquired drug resistance have led to the rise of highly pathogenic superbug bacterial strains for which treatment with first line drugs is no match. More than ever, there is a dire need for antibacterial drug design that goes beyond conventional standards. Taking inspiration by the body's innate immune response to employ its own supply of labile copper ions in a toxic attack against pathogenic bacteria, which have a very low Cu tolerance, this review article examines the feasibility of Cu-centric strategies for antibacterial preventative and therapeutic applications. Promising results are shown for the use of Cu-containing materials in the hospital setting to minimize patient bacterial infections. Studies directed at disrupting bacterial Cu regulatory pathways elucidate new drug targets that can enable toxic increase of Cu levels and perturb bacterial dependence on iron. Likewise, Cu intracellular chelation/prochelation strategies effectively induce bacterial Cu toxicity. Cu-based small molecules and nanoparticles demonstrate the importance of the Cu ions in their mechanism and display potential synergism with classical drugs.

A Highly Substituted Ring-Fused 2-Pyridone Compound Targeting PrfA and the Efflux Regulator BrtA in Listeria monocytogenes.

Listeria monocytogenes is a facultative Gram-positive bacterium that causes listeriosis, a severe foodborne disease. We previously discovered that ring-fused 2-pyridone compounds can decrease virulence factor expression in Listeria by binding and inactivating the PrfA virulence activator. In this study, we tested PS900, a highly substituted 2-pyridone that was recently discovered to be bactericidal to other Gram-positive pathogenic bacteria, such as Staphylococcus aureus and Enterococcus faecalis. We show that PS900 can interact with PrfA and reduce the expression of virulence factors. Unlike previous ring-fused 2-pyridones shown to inactivate PrfA, PS900 had an additional antibacterial activity and was found to potentiate sensitivity toward cholic acid. Two PS900-tolerant mutants able to grow in the presence of PS900 carried mutations in the brtA gene, encoding the BrtA repressor. In wild-type (WT) bacteria, cholic acid binds and inactivates BrtA, thereby alleviating the expression of the multidrug transporter MdrT. Interestingly, we found that PS900 also binds to BrtA and that this interaction causes BrtA to dissociate from its binding site in front of the mdrT gene. In addition, we observed that PS900 potentiated the effect of different osmolytes. We suggest that the increased potency of cholic acid and osmolytes to kill bacteria in the presence of PS900 is due to the ability of the latter to inhibit general efflux, through a yet-unknown mechanism. Our data indicate that thiazolino 2-pyridones constitute an attractive scaffold when designing new types of antibacterial agents. IMPORTANCE Bacteria resistant to one or several antibiotics are a very large problem, threatening not only treatment of infections but also surgery and cancer treatments. Thus, new types of antibacterial drugs are desperately needed. In this work, we show that a new generation of substituted ring-fused 2-pyridones not only inhibit Listeria monocytogenes virulence gene expression, presumably by inactivating the PrfA virulence regulator, but also potentiate the bactericidal effects of cholic acid and different osmolytes. We identified a multidrug repressor as a second target of 2-pyridones. The repressor-2-pyridone interaction displaces the repressor from DNA, thus increasing the expression of a multidrug transporter. In addition, our data suggest that the new class of ring-fused 2-pyridones are efficient efflux inhibitors, possibly explaining why the simultaneous addition of 2-pyridones together with cholic acid or osmolytes is detrimental for the bacterium. This work proves conclusively that 2-pyridones constitute a promising scaffold to build on for future antibacterial drug design.

Machine learning in antibacterial discovery and development: A bibliometric and network analysis of research hotspots and trends

Machine learning (ML) methods are used in cheminformatics processes to predict the activity of an unknown drug and thus discover new potential antibacterial drugs. This article conducts a bibliometric study to analyse the contributions of leading authors, universities/organisations and countries in terms of productivity, citations and bibliographic linkage. A sample of 1596 Scopus documents for the period 2006–2022 is the basis of the study. In order to develop the analysis, bibliometrix R-Tool and VOSviewer software were used. We determined essential topics related to the application of ML in the field of antibacterial development (Computer model in antibacterial drug design, and Learning algorithms and systems for forecasting). We identified obsolete and saturated areas of research. At the same time, we proposed emerging topics according to the various analyses carried out on the corpus of published scientific literature (Title, abstract and keywords). Finally, the applied methodology contributed to building a broader and more specific “big picture” of ML research in antibacterial studies for the focus of future projects.

Gold(I) selenium N-heterocyclic carbene complexes as potent antibacterial agents against multidrug-resistant gram-negative bacteria via inhibiting thioredoxin reductase

Multidrug-resistant (MDR) Gram-negative bacteria have become a global threat to human life and health, and novel antibiotics are urgently needed. The thioredoxin (Trx) system can be used as an antibacterial target to combat MDR bacteria. Here, we found that two active gold(I) selenium N-heterocyclic carbene complexes H7 and H8 show more promising antibacterial effects against MDR bacteria than auranofin. Both H7 and H8 irreversibly inhibit the bacterial TrxR activity via targeting the redox-active motif, abolishing the capacity of TrxR to quench reactive oxygen species (ROS) and finally leading to oxidative stress. The increased cellular superoxide radical levels impact a variety of functions necessary for bacterial survival, such as cellular redox balance, cell membrane integrity, amino acid metabolism, and lipid peroxidation. In vivo data present much better antibacterial activity of H7 and H8 than auranofin, promoting the wound healing and prolonging the survival time of Carbapenem-resistant Acinetobacter baumannii (CRAB) induced peritonitis. Most notably in this study, we revealed the influence of gold(I) complexes on both the Trx system and the cellular metabolic states to better understand their killing mechanism and to support further antibacterial drug design.

Benzoquinoline Chemical Space: A Helpful Approach in Antibacterial and Anticancer Drug Design.

Benzoquinolines are used in many drug design projects as starting molecules subject to derivatization. This computational study aims to characterize e benzoquinone drug space to ease future drug design processes based on these molecules. The drug space is composed of all benzoquinones, which are active on topoisomerase II and ATP synthase. Topological, chemical, and bioactivity spaces are explored using computational methodologies based on virtual screening and scaffold hopping and molecular docking, respectively. Topological space is a geometrical space in which the elements composing it can be defined as a set of neighbors (which satisfy a particular axiom). In such space, a chemical space can be defined as the property space spanned by all possible molecules and chemical compounds adhering to a given set of construction principles and boundary conditions. In this chemical space, the potentially pharmacologically active molecules form the bioactivity space. Results show a poly-morphological chemical space that suggests distinct characteristics. The chemical space is correlated with properties such as steric energy, the number of hydrogen bonds, the presence of halogen atoms, and membrane permeability-related properties. Lastly, novel chemical compounds (such as oxadiazole methybenzamide and floro methylcyclohexane diene) with drug-like potential, active on TOPO II and ATP synthase have been identified.

Molecular docking, dynamics simulation and pharmacokinetic studies of Cyperus articulatus essential oil metabolites as inhibitors of Staphylococcus aureus

Cyperus articulatus has been extensively studied for its essential oil (EO), active components and antibacterial activities against a wide range of bacteria such as Bacillus megaterium, Streptococcus pyogenes, Staphylococcus epidermidis, Escherichia coli and Staphylococcus aureus. However, knowledge of the biomolecular interaction of the individual EO metabolites responsible for its inhibition activities is lacking. The multi-drug-resistant bacteria S. aureus, which is of prime concern, has been reported to be inhibited by Cyperus articulatus rhizome EO. The present work analyzed the molecular interactions of the major Cyperus articulatus rhizome EO metabolites with the target enzyme TyrRS of S. aureus and studied the conformational dynamics and stability of the protein-ligand complexes. Molecular docking studies of selected EO metabolites such as mustakone, longifolenaldehyde, cyperotundone, α-copaene, β-calacorene, α-calacorene and khusinol were conducted along with standard drug chloramphenicol for comparative analysis of their binding affinity with S. aureus TyrRS. The metabolites khusinol, mustakone, β-calacorene and α-calacorene generated comparable docking scores (−6.4, −6.2, −6.1 and −6.2 kcal/mol, respectively) with that of the drug chloramphenicol (−6.3 kcal/mol). Most EO metabolites did not exhibit H-bonding with the S. aureus TyrRS residues and were stabilized through pi-interactions. The MD simulation study illustrated that compounds like mustakone could effectively bind to the receptors of S. aureus TyrRS with high stability and integrity. Pharmacokinetic, drug-like properties and toxicity analysis of the EO metabolites supported the candidature of mustakone and khusinol as pharmacologically important antibacterial drug ingredients. The study envisaged the structural framework of the EO metabolites for antibacterial drug design. Communicated by Ramaswamy H. Sarma

DeePVP: Identification and classification of phage virion proteins using deep learning.

BackgroundMany biological properties of phages are determined by phage virion proteins (PVPs), and the poor annotation of PVPs is a bottleneck for many areas of viral research, such as viral phylogenetic analysis, viral host identification, and antibacterial drug design. Because of the high diversity of PVP sequences, the PVP annotation of a phage genome remains a particularly challenging bioinformatic task.FindingsBased on deep learning, we developed DeePVP. The main module of DeePVP aims to discriminate PVPs from non-PVPs within a phage genome, while the extended module of DeePVP can further classify predicted PVPs into the 10 major classes of PVPs. Compared with the present state-of-the-art tools, the main module of DeePVP performs better, with a 9.05% higher F1-score in the PVP identification task. Moreover, the overall accuracy of the extended module of DeePVP in the PVP classification task is approximately 3.72% higher than that of PhANNs. Two application cases show that the predictions of DeePVP are more reliable and can better reveal the compact PVP-enriched region than the current state-of-the-art tools. Particularly, in the Escherichia phage phiEC1 genome, a novel PVP-enriched region that is conserved in many other Escherichia phage genomes was identified, indicating that DeePVP will be a useful tool for the analysis of phage genomic structures.ConclusionsDeePVP outperforms state-of-the-art tools. The program is optimized in both a virtual machine with graphical user interface and a docker so that the tool can be easily run by noncomputer professionals. DeePVP is freely available at https://github.com/fangzcbio/DeePVP/.

Machine Learning in Antibacterial Drug Design.

Advances in computer hardware and the availability of high-performance supercomputing platforms and parallel computing, along with artificial intelligence methods are successfully complementing traditional approaches in medicinal chemistry. In particular, machine learning is gaining importance with the growth of the available data collections. One of the critical areas where this methodology can be successfully applied is in the development of new antibacterial agents. The latter is essential because of the high attrition rates in new drug discovery, both in industry and in academic research programs. Scientific involvement in this area is even more urgent as antibacterial drug resistance becomes a public health concern worldwide and pushes us increasingly into the post-antibiotic era. In this review, we focus on the latest machine learning approaches used in the discovery of new antibacterial agents and targets, covering both small molecules and antibacterial peptides. For the benefit of the reader, we summarize all applied machine learning approaches and available databases useful for the design of new antibacterial agents and address the current shortcomings.

Experimental and Molecular Docking Studies of Cyclic Diphenyl Phosphonates as DNA Gyrase Inhibitors for Fluoroquinolone-Resistant Pathogens.

DNA gyrase and topoisomerase IV are proven to be validated targets in the design of novel antibacterial drugs. In this study, we report the antibacterial evaluation and molecular docking studies of previously synthesized two series of cyclic diphenylphosphonates (1a–e and 2a–e) as DNA gyrase inhibitors. The synthesized compounds were screened for their activity (antibacterial and DNA gyrase inhibition) against ciprofloxacin-resistant E.coli and Klebsiella pneumoniae clinical isolates having mutations (deletion and substitution) in QRDR region of DNA gyrase. The target compound (2a) that exhibited the most potent activity against ciprofloxacin Gram-negative clinical isolates was selected to screen its inhibitory activity against DNA gyrase displayed IC50 of 12.03 µM. In addition, a docking study was performed with inhibitor (2a), to illustrate its binding mode in the active site of DNA gyrase and the results were compatible with the observed inhibitory potency. Furthermore, the docking study revealed that the binding of inhibitor (2a) to DNA gyrase is mediated and modulated by divalent Mg2+ at good binding energy (–9.08 Kcal/mol). Moreover, structure-activity relationships (SARs) demonstrated that the combination of hydrazinyl moiety in conjunction with the cyclic diphenylphosphonate based scaffold resulted in an optimized molecule that inhibited the bacterial DNA gyrase by its detectable effect in vitro on gyrase-catalyzed DNA supercoiling activity.

Phytochemical Screening and Antibacterial Activity of Dendrobium from Papua Against Eschericia coli and Staphylococcus aureus

Orchid found as one of medicinal plant in some areas, especially Dendrobium. Some species were investigated its bioactive compound, and antibacterial activity, but the information about antibacterial activity of Papuan Dendrobium species is still limited. The aims of this research were to determine the phytochemical constituents and the antibacterial activity of ethanolic extract and fraction of Dendrobium species from Papua against Escherichia coli and Staphylococcus aureus. There were three species of Dendrobium namely: D. spectabile, D. violaceoflavens, and D. antennatum used in this study. Dried simplisia was macerated using ethanol, then tested for the phytochemical content. Total ethanolic extract was fractionated with three different solvents, ethanol, ethyl acetate and hexane. Disc diffusion assay was used to examine the antibacterial activities of the total extract and the fractions. Total extract were positive for flavonoid, alkaloid and tanin, except D. spectabile stem extract only alkaloid and tannin. No saponin was found in the plants. The ethyl acetate fraction of leaves of D. spectabile showed the highest antibacterial activity against S. aureus with diameter of inhibition zone 20.54 + 1.47 mm (strong category). Other plant extract and fraction tested had moderate antibacterial activities against both E.coli and S aureus with diameter zone 6-9 mm. The present work indicates that the ethyl acetate fraction of D. spectabile leaves is potential to be developed in antibacterial drug design research.  Key words: antibacterial activity; Papua; Dendrobium; E. coli; S. aureus.Â

Co-delivery of ampicillin and β-lactamase inhibitor by selenium nanocomposite to achieve synergistic anti-infective efficiency through overcoming multidrug resistance

Bacterial infective diseases due to antibiotic resistance remain a great challenge in clinic. Design of novel antibacterial drugs with high efficiency and low side effects to overcome antibiotic resistance is urgently needed. Herein, M-Cs (mannose- modified chitosan) modified selenium (Se) nanoparticles to co-deliver ampicillin (Ap) and β-lactamase inhibitor were synthesized and characterized (SAMCP NPs). Mannose modification endowed SAMCP NPs with enhanced recognition of bacteria by FimH lectin. Co-delivery of ampicillin and β-lactamase inhibitor (3-carboxyphenylboronic acid, Pba) by selenium nanocomposite (30 μg/mL) effectively inhibited β-lactamase activity, which synergistically enhanced ampicillin-induced antibacterial activity against ampicillin-resistant Escherichia coli (E. coli (R)) in vitro by suppression of AcrAB-TolC efflux pump system through eliminating ROS. SAMCP NPs (5 mg/kg) in vivo also showed synergistic anti-infective efficiency by inhibiting E. coli (R) infection-induced inflammatory response, cell apoptosis and regulating multiple signal pathways, and eventually promoted wound healing of mice. Importantly, SAMCP NPs displayed low toxicity and low side effects in vivo. Our findings validated our rational design that co-delivery of ampicillin and β-lactamase inhibitor by selenium nanocomposite to overcome multidrug resistance could be a highly efficient way to achieve antibacterial synergy.

Fluorothiazinon, a small-molecular inhibitor of T3SS, suppresses salmonella oral infection in mice.

Therapeutic strategies that target bacterial virulence have received considerable attention. The type III secretion system (T3SS) is important for bacterial virulence and represents an attractive therapeutic target. Recently, we developed a new small-molecule inhibitor belonging to a class 2,4-disubstituted-4H-[1,3,4]-thiadiazine-5-ones, Fluorothiazinon (FT-previously called CL-55). FT effectively suppressed T3SS of Chlamydia spp., Pseudomonas aeruginosa, and Salmonella without affecting bacterial growth in vitro. FT was previously characterized by low toxicity, stability, and therapeutic efficacy in animal models. Salmonella T3SS inhibition by FT was studied using in vitro assays for effector proteins detection and estimation of salmonella replication in peritoneal macrophages. The antibacterial effect of FT in vivo was investigated in murine models of salmonella chronic systemic and acute infection. Oral administration of the virulent strain of Salmonella enterica serovar Typhimurium to mice-induced chronic systemic infection with the pathogen persistence in different lymphoid organs such as spleens, Peyer's plaques, and mesenteric lymph nodes. We found that FT suppressed orally induced salmonella infection both with therapeutic and prophylactic administration. Treatment by FT at a dose of 50 mg/kg for 4 days starting from day 7 post-infection (therapy) as well as for 4 days before infection (prevention) led to practically complete eradication of salmonella in mice. FT shows a strong potential for antibacterial therapy and could be used as a substance in the design of antibacterial drugs for pharmaceutical intervention including therapy of antibiotic-resistant infections.

Revealing the Dynamic Allosteric Changes Required for Formation of the Cysteine Synthase Complex by Hydrogen-Deuterium Exchange MS

CysE and CysK, the last two enzymes of the cysteine biosynthetic pathway, engage in a bienzyme complex, cysteine synthase, with yet incompletely characterized three-dimensional structure and regulatory function. Being absent in mammals, the two enzymes and their complex are attractive targets for antibacterial drugs. We have used hydrogen/deuterium exchange MS to unveil how complex formation affects the conformational dynamics of CysK and CysE. Our results support a model where CysE is present in solution as a dimer of trimers, and each trimer can bind one CysK homodimer. When CysK binds to one CysE monomer, intratrimer allosteric communication ensures conformational and dynamic symmetry within the trimer. Furthermore, a long-range allosteric signal propagates through CysE to induce stabilization of the interface between the two CysE trimers, preparing the second trimer for binding the second CysK with a nonrandom orientation. These results provide new molecular insights into the allosteric formation of the cysteine synthase complex and could help guide antibacterial drug design.

Antibacterial Activity of Fluorobenzoylthiosemicarbazides and Their Cyclic Analogues with 1,2,4-Triazole Scaffold.

The development of drug-resistant bacteria is currently one of the major challenges in medicine. Therefore, the discovery of novel lead structures for the design of antibacterial drugs is urgently needed. In this structure–activity relationship study, a library of ortho-, meta-, and para-fluorobenzoylthiosemicarbazides, and their cyclic analogues with 1,2,4-triazole scaffold, was created and tested for antibacterial activity against Gram-positive bacteria strains. While all tested 1,2,4-triazoles were devoid of potent activity, the antibacterial response of the thiosemicarbazides was highly dependent on substitution pattern at the N4 aryl position. The optimum activity for these compounds was found for trifluoromethyl derivatives such as 15a, 15b, and 16b, which were active against both the reference strains panel, and pathogenic methicillin-sensitive and methicillin-resistant Staphylococcus aureus clinical isolates at minimal inhibitory concentrations (MICs) ranging from 7.82 to 31.25 μg/mL. Based on the binding affinities obtained from docking, the conclusion can be reached that fluorobenzoylthiosemicarbazides can be considered as potential allosteric d-alanyl-d-alanine ligase inhibitors.

Antimicrobial and cytotoxic effects of ammonium derivatives of diterpenoids steviol and isosteviol

Antimicrobial and cytotoxic activities of several ammonium derivatives of diterpenoids steviol and isosteviol have been investigated in vitro. The results have showed that these compounds possess high antibacterial activity against MRSA strains and cytotoxic effect against cancer cell lines MCF-7, M−HeLa, A-549, PC3, HepG2, T98G. Lead compounds 4 and 5 were detected, which, in the case of the MCF-7 cell line (human breast adenocarcinoma), showed IC50 at the doxorubicin level with a selectivity index of 5.0–5.2. Flow cytometry and laser confocal microscopy analysis demonstrated that the mechanism of cytotoxic effects of the tested compounds on MCF-7 cells could be associated with the induction of apoptosis along the mitochondrial pathway. At the same time, they did not cause hemolysis and showed only slight cytotoxicity with respect to normal human cells of embryonic lung (Wi-38).The obtained results allow us to consider the studied compounds as promising scaffolds for the design of new effective antibacterial drugs and anticancer agents targeting mitochondria.

RETRACTED: Embedded medical platform hardware design and application of antibacterial drugs for respiratory infections

The combination of cloud computing and medicine, telemedicine, post-discharge care plan, and such virtual compliance with the drug can improve many medical-related functions. Also, to improve access to healthcare services through telemedicine. The reader to their various application types of the medical field and the processor before this. Description of peripheral equipment and tools to be used in embedded systems are also discussed here. Our focus is the medical equipment of the new era, and we, too, contains some of the existing medical equipment. A variety of bacterial infections is a significant problem for humans and a health threat. Revealing antimicrobial compounds' interactions with a biological agent has stimulated scientists to find new solutions to treat these diseases. (Personal Computer) PC, smartphone, tablet, wearable. Cloud computing technology access storage through a device connected to the Internet and files, software, and on the server to enable the user. Where the cloud computing providers store and process data are separated from the end-user. Antibiotics are rarely as long and not required to treat upper respiratory tract infections that doctors do not suspect a bacterial infection; you should generally avoid. In this way, a simple, such as to cover the surface properly wash their hand's technology, while coughing or sneezing, you can reduce the spread of respiratory infections. It will introduce some basic concepts related to antimicrobial agents. Novel compounds describe the correlation between the activity in vitro and in vivo synthetic path way and antibacterial substances specific design techniques, and polymeric materials. Mechanism of action, and efficacy in vivo, its raw data is reviewed about selecting antimicrobial resistance mechanisms most commonly used.