Effective Antimicrobial Drugs Research Articles

In silico Molecular Docking of Cyclic Peptides against TEM-1 Beta-Lactamases for Effective Antimicrobial Drug Development

Targeting the class A Beta lactamases Omega loop is an ideal way to combat drug resistance because of its significant role in the catalytic activity and deacylation process inhibition. Therefore, the molecular docking approach with computerized peptide-based in silico screening has been applied for the identification of inhibitors of TEM-type βLs. Among the subjected 105 peptides, Chrombacin (-47.8 KJ/mol), Gassericin A (-35.7 KJ/mol), Duramycin (-34.1 KJ/mol), Brevinin-1DYa (-34.0 KJ/mol), Amoebapore A (-31.2 KJ/mol), Mundticin ATO6 (-29.0 KJ/mol), Lactocyclicin Q (-26.3 KJ/mol), Cinnamycin (-25.9 KJ/mol showed highest binding energy. Among the peptides that showed the highest docking score Elafin, Cinnamycin, Duramycin interacted with Lys 73 of the α domain of catalytic residues of TEM-1 Beta lactamases, whereas Taromycin A, Gassericin A interacted with Lys 234 of the β domain, depicting a strong inhibition and also exhibited desirable physicochemical properties. Hence further in vitro examination of these cyclic peptides against the resistant strains is warranted to help design further novel inhibitors based on their scaffolds and also for the development of an effective drug combination regime.

Synthesis and invitro evaluation of antibacterial and antibiofilm activities of novel triphenylphosphonium-functionalized substituted pyrimidines.

The increase in the prevalence of antibiotic-resistant pathogens leads to a decrease in the number of antimicrobial agents for the treatment of infections and prompts researchers to search for new effective antimicrobial drugs. This study reports the synthesis of novel triphenylphosphonium-functionalized substituted pyrimidines and invitro evaluation of their antibacterial and antibiofilm activity. Most of the synthesized derivatives showed high antibacterial activity (MIC = 0.39-1.56 μg/mL) against the methicillin-resistant strain of S. aureus 222. Compounds 2a and 11 exhibited a high level of antibiofilm activity against S. aureus 222 and E. coli 311. The triphenylphosphonium-containing pyrimidines 11 and 2a reduced S. aureus 222 biofilm formation by 99.1% and 95.8%, respectively. In addition, compound 2a was the most active against E. coli 311 biofilm formation (the biomass decreased by 98.4%).

Ferrocene-bisphosphonates hybrid drug molecules: In vitro antibacterial and antifungal, in silico ADME, drug-likeness, and molecular docking studies

The design of hybrid molecules is a promising drug development strategy to prepare effective antimicrobial drugs that employ the concept of combination therapy. This strategy combines two therapeutic agents covalently to target different cellular pathways for synergistic effects. Ferrocene-bisphosphonate hybrid compounds, 1–8 were evaluated in vitro for their antibacterial and antifungal activities against selected fungal strains, gram-positive, and gram-negative bacteria. Hybrid compounds, 5, 6, and 8 exhibited significant antibacterial activity against all the bacterial strains than the control, fosfomycin with the lowest MIC value of ≤ 3 against Proteus mirabilis and Klebsiella aerogenes. The antifungal activity of hybrids, 2, 4, 5, and 6 against Penicillum Citrinum and Aspergillus ochraceus was high when compared to the control, nystatin. The lowest MIC values were 107 and 214 µM against Penicillum Citrinum and Aspergillus ochraceus for hybrid 5. The molecular docking studies revealed the inhibition of urease enzymes in Klebsiella aerogenes with a high binding energy of −3.973 and −4.645 Kcal/mol, respectively for hybrids 5 and 6. The in silico toxicity revealed the non-toxic effects of the hybrid compounds. The SwissADME parameters of the hybrid molecules further predicted good permeability, water solubility, and oral bioavailability, inability to cross the blood–brain barrier (BBB) and non-inhibition effects on some CYP isoenzymes, suggesting that their biotransformation will not be via the cytochrome isoenzymes. Most of the hybrids, 4–8 were predicted to be P-glycoprotein substrates. The hybrids obeyed Lipinski's rules with one violation, the Ghose rule, and the Egan rule. These findings indicate that the efficacy of hybrid compounds as promising antimicrobials and future studies are needed.

Antimicrobial efficacy of Tejpata

Treatment with antibiotics became so common that people start using these drugs even for the little of ailment resulting in misuse of antibiotics. This leads to decrease in susceptibility of microorganisms to the present antibiotics or antimicrobial agents. Currently, in addition to antibiotics and chemically synthesized drugs, the trend to look out for alternative medicines such as natural or herbal medicines is increasing because of fewer side effects or toxicity owing to their natural sources. Therefore, the need for novel / more effective antimicrobial drugs, is an absolute necessity and remains a very important area of research against pathogens. In the present study, antifungal and antibacterial effect of leaves has been evaluated against three fungal and five bacterial strains via methanolic extract. showed moderate growth inhibition against the fungal strain The methanolic extract of the leaves of the plantalsoshowed average activity against the three bacterial strains viz., and .

Efficient Delivery of Antimicrobial Peptides in an Innovative, Slow-Release Pharmacological Formulation.

Both nanostructure and multivalency enhance the biological activities of antimicrobial peptides (AMPs), whose mechanism of action is cooperative. In addition, the efficacy of a particular AMP should benefit from a steady concentration at the local place of action and, therefore, from a slow release after a dynamic repository. In the context of emerging multi-resistant bacterial infections and the urgent need for novel and effective antimicrobial drugs, we tested these concepts through the engineering of four AMPs into supramolecular complexes as pharmacological entities. For that purpose, GWH1, T22, Pt5, and PaD, produced as GFP or human nidogen-based His-tagged fusion proteins, were engineered as self-assembling oligomeric nanoparticles ranging from 10 to 70 nm and further packaged into nanoparticle-leaking submicron granules. Since these materials slowly release functional nanoparticles during their time-sustained unpacking, they are suitable for use as drug depots in vivo. In this context, a particular AMP version (GWH1-NIDO-H6) was selected for in vivo validation in a zebrafish model of a complex bacterial infection. The GWH1-NIDO-H6-secreting protein granules are protective in zebrafish against infection by the multi-resistant bacterium Stenotrophomonas maltophilia, proving the potential of innovative formulations based on nanostructured and slowly released recombinant AMPs in the fight against bacterial infections.

Incorporating isoniazid in clay minerals as a mean of leveraging drug effectiveness: A study review

Tuberculosis is a globally widespread infectious disease with elevated transmissibility and expressive mortality rate. It affects people throughout all age groups causing a strong economic impact on public health systems. Isoniazid, which was launched in the market in the 60’s, has been the most effective antimicrobial drug for the treatment of tuberculosis so far. However, this is a long treatment with many adverse effects resulting in poor patient compliance. Therefore, it is necessary to develop oral intake systems that minimize the adverse effects of the drug to guarantee patients adherence to the treatment. Over the last decade, extensive research has shown that the development of controlled release systems is an effective way of addressing isoniazid’s adverse effects. The intercalation of isoniazid in clay minerals such as bentonites present highly promising results. The present study review seeks to summarize and allow readers to understand the most recent published articles and research on this subject.

Antibacterial and antibiofilm efficacy of colistin & meropenem conjugated silver nanoparticles against Escherichia coli and Klebsiella pneumoniae.

The progressive increase in infections caused by multidrug-resistant (MDR) Gram-negative bacteria and the emergence of resistance to last-resort antimicrobial drugs in recent years necessitate the development of new therapeutic strategies. This study was conducted to obtain nanostructured antimicrobials by conjugating colistin (COL) and meropenem (MEM) antibiotics with biosynthesized silver nanoparticles (bio-AgNPs) via the green synthesis method using Rosa damascena extract, and to investigate the antibacterial and antibiofilm activity of these nanostructures against Escherichia coli and Klebsiella pneumoniae strains. Ultraviolet-visible spectrophotometry, high-resolution-transmission electron microscopy, atomic force microscopy, X-ray diffraction, and Fourier transform-infrared spectroscopy analyses were performed to determine the physical and chemical properties of synthesized bio-AgNPs, COL@bio-AgNPs, MEM@bio-AgNPs, and COL&MEM@bio-AgNPs. The minimum inhibitory concentration (MIC) and minimum bactericidal concentration of nanoparticles were determined on standard and MDR clinical strains. The antibiofilm efficacy and cytotoxic effect of nanoparticles were evaluated by the crystal violet dye method and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide dye method, respectively. The characterization analyses demonstrated that the synthesized nanoparticles had crystal structure and spherical morphology (5.6-30.2 nm in size). Antibiotic conjugated nanoparticles exhibited better antimicrobial activity and lower MIC values (0.125-4 µg/mL) on the tested strains compared to free antibiotics, and MIC values were decreased up to 1024-fold (p < 0.05). Antibiotic conjugated nanoparticles were found to be more effective in biofilm eradication than free antibiotics and bio-AgNPs and had a less inhibitory effect on peripheral blood mononuclear cell viability. The findings revealed that antibiotic-conjugated nanoparticles have the potential to be used as an effective antimicrobial drug against MDR E. coli and K. pneumoniae strains.

Introducing of novel class of pyrano[2,3-c]pyrazole-5-carbonitrile analogs with potent antimicrobial activity, DNA gyrase inhibition, and prominent pharmacokinetic and CNS toxicity profiles supported by molecular dynamic simulation

Microbiological DNA gyrase is recognized as an exceptional microbial target for the innovative development of low-resistant and more effective antimicrobial drugs. Hence, we introduced a one-pot facile synthesis of a novel pyranopyrazole scaffold bearing different functionalities; substituted aryl ring, nitrile, and hydroxyl groups. All new analogs were characterized with full spectroscopic data. The antimicrobial screening for all analogs was assessed against standard strains of Gm + ve and Gm-ve through in vitro considers. The screened compounds displayed very promising MIC/MBC values against some of the bacterial strains with broad or selective antibacterial effects. Of these, 4j biphenyl analog showed 0.5-2/2-8 µg/mL MIC/MBC for suppression and killing of Gm + ve and Gm-ve strains. Moreover, the antimicrobial screening was assessed for the most potent analogs against certain highly resistant microbial strains. Consequently, DNA gyrase supercoiling assay was done for all analogs using ciprofloxacin as reference positive control. Obviously, the results showed a different activity profile with potent analog 4j with IC50 value 6.29 µg/mL better than reference drug 10.2 µg/mL. Additionally, CNS toxicity testing was done using the HiB5 cell line for attenuation of GABA/NMDA expression to both 4j and ciprofloxacin compounds that revealed better neurotransmitter modulation by novel scaffold. Importantly, docking and dynamic simulations were performed for the most active 4j analog to investigate its interaction with DNA binding sites, which supported the in vitro observations and compound stability with binding pocket. Finally, a novel scaffold pyranopyrazole was introduced as a DNA gyrase inhibitor with prominent antibacterial efficacy and low CNS side effect toxicity better than quinolones. Communicated by Ramaswamy H. Sarma

Anti-MRSA activity of Stereospermum fimbriatum’s stem bark extracted using subcritical and supercritical carbon dioxide

Antibiotic resistance is a major challenge in healthcare, and this is further worsened by the presence of the dreadful Methicillin-resistant Staphylococcus aureus (MRSA) infection. This has urged scientists to find new effective antimicrobial drugs. Earth is enriched with natural resources such as plants that have been used traditionally to cure diseases. Stereospermum fimbriatum or “Chicha” had been used traditionally to treat several illnesses such as stomachache, earache, itchy skin, and postpartum illness. Thus, this study was designed to investigate the antibacterial potential of S. fimbriatum’s stem bark against MRSA. Subcritical (Sub-CO2) and supercritical carbon dioxide (Sup-CO2) extractions were used to extract the stem bark, with and without the addition of co-solvent (ethanol). The antimicrobial assay was carried out using disc diffusion (200, 400 and 600 µg/disc), minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) tests. There was no anti-MRSA activity observed on both the Sub-CO2 and Sup-CO2 extracts without 10% ethanol. The most potent anti-MRSA was observed by the Sup-CO2 extract with 10% ethanol with the MIC value of 500 µg/mL. Therefore, the use of ethanol (10 %) in the extraction increased the antibacterial activity of the S. fimbriatum’s extract against MRSA. These research findings could potentially facilitate future investigations into the utilization of green extraction methods to uncover promising antibacterial agents that can effectively target MRSA, a formidable pathogen. Future studies on the other parts of S. fimbriatum, its potential toxicity, and the possible mechanisms of action are needed to investigate its promising therapeutic values on MRSA infections.

Antimicrobial Effect of Silver Nanoparticles and Combination with Cotrimoxazole against Salmonella Typhi in Vitro and in Animal Model

Introduction: Salmonella typhi is a large group of gram-negative bacilli with Enterobacteriaceae and common pathogens between humans and animals, which is the main cause of typhoid fever in humans. One of the most common antibiotics in the treatment of Salmonella is cotrimoxazole, but due to the widespread use of antibiotics, bacterial resistance has developed. The aim of this study was to investigate the antibacterial effect of silver nanoparticles and its combination with the antibiotic cotrimoxazole to produce a more effective antimicrobial drug against Salmonell typhi.&#x0D; Methods: In this experimental study, the minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) for silver nanoparticles and combination with cotrimoxazole, was performed based on microdilution method. Then, their antibacterial effects were investigated in infected mouse model. In order to analyze the results statistically, SPSS software version 16 was used. In this test, P&lt; 0.05 was considered as a significant level.&#x0D; Results: MIC and MFC of silver nanoparticles for Salmonella typhi were 4 ppm and 8 ppm respectively, composition of silver nanoparticles with cotrimoxazole for Salmonella typhi were 62 ppm and 125 ppm and cotrimoxazole for Salmonella typhi were 500 ppm and 1000 ppm. Mouse model to study the antibacterial effect of silver nanoparticles and combination with cotrimoxazole against Salmonella typhi infection was confirmed., Silver nanoparticles had the highest antibacterial effect and cotrimoxazole has the lowest antibacterial effect than other groups.&#x0D; Conclusion: Silver nanoparticles are very effective compared to other groups, especially the antibacterial cotrimoxazole.

In Silico Studies, Design and Synthesis of Novel Fused Pyrimidine Derivatives as a DNA Gyrase Inhibitor and Antibacterial Activity Against Quinolone Resistant Escherichia Coli

In recent years, antimicrobial agents have been crucial in improving public health worldwide. However, due to improper usage, bacteria have developed resistance to these agents. This has led researchers to explore the use of heterocyclic compounds as alternative antimicrobial agents to combat resistance. Considering the success of heterocyclic derivatives in developing effective antimicrobial drugs, we conducted a 2D-QSAR (QSAR models using 2D-descriptors) study on novel pyrimidine derivatives and performed in silico simulations to evaluate their potential antibacterial activity against quinolone-resistant Escherichia coli. We used QSARINS V.2.2 (Insubria) software for the 2D-QSAR analysis and performed in silico absorption, distribution, metabolism, and excretion (ADME) and docking studies on 16 newly designed compounds. The best QSAR model had a high correlation coefficient ([Formula: see text], [Formula: see text], [Formula: see text]) and showed no outliers. Based on these favorable results, we designed 16 new compounds and predicted their antibacterial activity using the best equation. Amongst the top six designed compounds, which had the best docking scores were subjected to practical synthesis. Compound 3cd was found to be good candidature from in-vitro anti-E. Coli activity. This compound may be targeting the DNA gyrases and thus, have inhibitory activity against E. Coli. This observation was also supported by 100[Formula: see text]ns molecular dynamics and normal mode analysis results. The most promising compounds identified through these computational studies may be synthesized and tested as potential new drug candidates for treating bacterial infections.

Approach to multidrug resistant bacterial infections

Several bacterial pathogens have evolved into multidrug resistant (MDR) forms both in developed and developing countries at an expanding rate. The World Health Organization has identified antimicrobial resistance as one of the three most important problems facing human health. It was estimated that 4·95 million deaths were associated with bacterial AMR globally in 2019.1 Three infectious syndromes dominated the global burdens attributable to AMR: lower respiratory and thorax infections, bloodstream infections, and intra-abdominal infections. Some of the most important MDR pathogens that currently cause infection in hospital and in the community are the so-called “ESKAPE” pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species), emphasizing their capacity to “escape” the effects of routine antibiotics. Most of the MDR studies were heterogeneous in terms of study design, patient population, site of infection, choice of antibiotic treatment, duration of followup period, and the outcome definitions, making it difficult to compare the different treatments and combinations of antibiotics used. Current recommendations in Europe and USA are based on systematic reviews that suggest different methods to prevent and control MDR infections, but provide little data on new and alternative antibiotic treatment options and therefore provide little firm guidance on specific treatment choices and algorithms. Attempts are ongoing to overcome antibacterial resistance by using new agents and combinations of new plus old agents. For example, both old (clavulanic acid, tazobactam) and new (avibactam, vaborbactam, relebactam) BLIs are being used in treatment algorithm for critically ill patients in the ICU according to MDR pathogen. There were still controversies regarding microbiological success for single agent compared with combinations of multiple agents. Many bacteria have the ability to produce biofilms, comprising organized congregations of bacteria adhering to each other making complex condition where antibiotic failed to wipe out bacteria despite of retaining in vitro susceptibility. It is also not always possible to conduct randomized controlled studies involving the required number of patients in a timely manner. So a requirement with the increasing choice of highly effective antimicrobial drugs, with dosages based on pharmacokinetic analysis of drug disposition, selection of the appropriate drug based on clinical microbiological data and pharmacodynamic indices. Rational antimicrobial therapy is more applicable today than in the history of antimicrobial therapy. Exploring newer modalities such as phage therapy and lytic antibiotics as well as obtaining a deeper understanding of the pathways involved in MDR mechanisms in order to engineer targeted drugs. Besides, rapid and comprehensive diagnostics are the key factor for the future management of antimicrobial resistance. Bangladesh J Medicine 2023; Vol. 34, No. 2(1) Supplement: 195-196

Quantitative determination of 4-((5-(decylthio)-4-methyl-4-h-1,2,4-triazol-3-yl)methyl)morpholine in the soft medicinal form by spectrophotometric method

Synthetic biologically active compounds are the active pharmaceutical ingredients of various dosage forms that are widely used in both human and veterinary medicine. Nowadays the development of new effective antimicrobial and antifungal drugs remains a actual problem. This fact has a reasoned explanation in connection with the increase in infectious diseases of microbial and fungal etiology and the ever-growing resistance of microorganisms and fungi to various drugs.&#x0D; The aim of this research was to develop and validate a new spectrophotometric method for the quantitative determination of 4-((5-(decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine in 7% ointment by intrinsic absorption.&#x0D; At the stage of development of the quantitative determination method, the solvent was selected based on the solubility of the active substance. According to the data provided, 4-((5-(decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine is insoluble in water, but soluble in ethanol, methanol, isopropanol, dioxane, and dimethyl sulfoxide. Ethanol was chosen as the most accessible and less toxic solvent for the development of this method. Studied 4-((5-(decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine dissolved in ethanol is introduced into the ointment base as a solution.&#x0D; The quantitative content of substances subject to chemical control in soft dosage forms should be between 90% and 110% of the nominal content. On this basis, the maximum permitted analytical uncertainty can be determined, which is 3.20.&#x0D; During the procedure the main validation characteristics were determined, such as: linearity, precision, accuracy and robustness.&#x0D; Thus, a new sensitive, economical and easy-to-use spectrophotometric method for the quantitative determination of 4-((5-(decylthio)-4-methyl-4-H-1,2,4-triazol-3-yl)methyl)morpholine in a soft dosage form for external use (7% ointment) by the intrinsic absorption method was developed. According to the main validation characteristics (linearity, precision, accuracy and robustness), the proposed method is valid and meets the requirements of the State Pharmacopoeia of Ukraine.

Prevalence of Multidrug Resistant Pseudomonas aeruginosa Isolated from Clinical Specimens in Tertiary Care Hospital.

Pseudomonas aeruginosa is an opportunistic pathogen, which causes nosocomial infections in human. The rapid increase in drug resistance of this pathogen is a global concern. The aim of this study was to determine the clinical burden of P.aeruginosa, its antibiotic susceptibility pattern along with metallo-β-lactamase (MBL) detection. The descriptive cross-sectional study was conducted in Upendra Devkota Memorial National Institute of Neurological and Allied Sciences from January to August 2021. Isolation and identification of P. aeruginosa from clinical specimens was performed by using standard laboratory procedure. All bacterial isolates were phenotypically screened for multidrug resistance using Kirby Bauer disc diffusion method. All the multidrug resistant P.aeruginosa were phenotypically screened for MBL producer by Imipenem-EDTA combined disc diffusion test (CDDT). A total of 770 samples were processed of which 36 isolates of P. aeruginosa were obtained. P.aeruginosa was isolated mainly from tracheal aspirates, sputum, blood and urine. Among 36 isolates, 50% were found to be multidrug resistant (MDR). More percentage of P.aeruginosa isolates were found resistant to aztreonam, ofloxacin and levofloxacin (52.8%). Furthermore, this study reveals antibiotics like piperacillin/tazobactam and carbapenem were found to be good choice for the treatment of infection caused by this organism. Among MDR isolates 66.7% were found to be MBL producer. The data in this study highlights the prevalence of multidrug resistant, MBL producer, and colistin resistant P.aeruginosa in clinical specimens. In this study, carbapenems and piperacillin/tazobactam were found to be most effective antimicrobial drugs for empirical therapy in P.aeruginosa infections.

Green Synthesis of Na abietate Obtained from the Salification of Pinus elliottii Resin with Promising Antimicrobial Action.

The growing concern about the emergence of increasingly antibiotic-r4esistant bacteria imposes the need to search and develop drugs to combat these microorganisms. This, combined with the search for low-cost synthesis methods, was the motivation for the elaboration of this work. Abietic acid present in the resin of Pinus elliotti var. elliotti was used to generate a sodium salt by salification. The synthesis route was low-cost, consisting of only two reaction steps at mild temperatures without toxic organic solvents, and eco-friendly and easy to conduct on an industrial scale. Sodium abietate (Na-C20H29O2) was characterized by mass spectrometry, infrared spectroscopy, elemental analysis, X-ray diffraction, scanning electron microscopy, and energy-dispersive spectroscopy. To perform the antimicrobial tests, the determination of minimum inhibitory concentration and the disk diffusion assay was performed. The results obtained showed that the salt Na abietate performed an antimicrobial action against the bacterial strains S. aureus, E. coli, L.monocytogenes, and S. enterica Typhimurium and the yeast C. albicans. The disk diffusion test showed a high inhibition potential against S. enterica compared to the standard antimicrobial tetracycline, as an inhibition index of 1.17 was found. For the other bacterial strains, the inhibition values were above 40%. The MIC test showed promising results in the inhibition of E. coli, L. monocytogenes, and C. albicans, indicating bacteriostatic activity against the first microorganism and bactericidal and fungicidal activities against the others. Therefore, the results showed the action of Na abietate as a possible effective antimicrobial drug, highlighting its sustainability within a circular economy.

Carbapenem-resistant Acinetobacter baumannii healthcare-associated infections: antimicrobial resistance and its spread as a global threat.

Carbapenem-resistant Acinetobacter baumannii healthcare-associated infections: antimicrobial resistance and its spread as a global threat.

Assessment of the phytochemical composition and antimicrobial properties of Tapinanthus bangwensis leaves hosted by the branches of Persea americana

BackgroundMedicinal plants represent a valuable source for new effective and safe antimicrobial drugs making them an alternative therapy. Existing antimicrobial agents are costly and mostly associated with possible side effects. The aim of the present study therefore, was to assess the antimicrobial property and phytochemical composition of hydroethanolic extract of Tapinanthus bangwensis leaves and its fractions.MethodT. bangwensis leaves (harvested from its host plant, Persea americana) was extracted by cold maceration with 70% ethanol and further fractionated with different organic solvents using the solvent partitioning method to obtain the crude extract, petroleum ether, chloroform, ethyl acetate and the resulting aqueous fractions. The phytochemical constituents of the extracts were screened and quantified. Also, the TLC of the extracts were analyzed to serve as a fingerprint. Using the agar diffusion and broth dilution methods, the antimicrobial properties of the extracts were assessed.ResultsThe study showed that the hydroethanolic (70%) crude extract of T. bangwensis leaves and its fractions contain phenolic compounds, flavonoids, saponins, phytosterols and reducing sugars. The phytoconstituents were well extracted into the ethyl acetate fraction than the other fractions evidenced in the high levels (p < 0.0001) of saponins (66.47 ± 1.72% w/w), phenolic compounds (77.75 ± 1.06 mg/100 mg GAE) and flavonoids (44.34 ± 0.06 mg/100 mg QE) contents. From the antimicrobial studies, all the microorganisms tested exhibited varying degrees of susceptibility to the extracts with MIC values between 0.78 to 12.5 mg/mL. The crude extract of T. bangwensis leaves, its ethyl acetate and chloroform fractions also exhibited lethal antimicrobial activity with MLC between 6.25 to 50 mg/mL.ConclusionThe crude extract of T. bangwensis leaves and its fractions demonstrated antimicrobial properties against Escherichia coli, Staphylococcus aureus, Staphylococcus saprophyticus and Candida albicans, thereby representing a potential source of natural antimicrobial agent. Further study is required to identify and isolate antimicrobial compounds from the plant for the development of the natural bioactive antimicrobial agents.

Gossypol acetate: A natural polyphenol derivative with antimicrobial activities against the essential cell division protein FtsZ.

Antimicrobial resistance has attracted worldwide attention and remains an urgent issue to resolve. Discovery of novel compounds is regarded as one way to circumvent the development of resistance and increase the available treatment options. Gossypol is a natural polyphenolic aldehyde, and it has attracted increasing attention as a possible antibacterial drug. In this paper, we studied the antimicrobial properties (minimum inhibitory concentrations) of gossypol acetate against both Gram-positive and Gram-negative bacteria strains and dig up targets of gossypol acetate using in vitro assays, including studying its effects on functions (GTPase activity and polymerization) of Filamenting temperature sensitive mutant Z (FtsZ) and its interactions with FtsZ using isothermal titration calorimetry (ITC), and in vivo assays, including visualization of cell morphologies and proteins localizations using a microscope. Lastly, Bacterial membrane permeability changes were studied, and the cytotoxicity of gossypol acetate was determined. We also estimated the interactions of gossypol acetate with the promising target. We found that gossypol acetate can inhibit the growth of Gram-positive bacteria such as the model organism Bacillus subtilis and the pathogen Staphylococcus aureus [both methicillin-sensitive (MSSA) and methicillin-resistant (MRSA)]. In addition, gossypol acetate can also inhibit the growth of Gram-negative bacteria when the outer membrane is permeabilized by Polymyxin B nonapeptide (PMBN). Using a cell biological approach, we show that gossypol acetate affects cell division in bacteria by interfering with the assembly of the cell division FtsZ ring. Biochemical analysis shows that the GTPase activity of FtsZ was inhibited and polymerization of FtsZ was enhanced in vitro, consistent with the block to cell division in the bacteria tested. The binding mode of gossypol acetate in FtsZ was modeled using molecular docking and provides an understanding of the compound mode of action. The results point to gossypol (S2303) as a promising antimicrobial compound that inhibits cell division by affecting FtsZ polymerization and has potential to be developed into an effective antimicrobial drug by chemical modification to minimize its cytotoxic effects in eukaryotic cells that were identified in this work.

ВЛИЯНИЕ ЦЕЛЕНАПРАВЛЕННО СИНТЕЗИРОВАННОГО АЗОМЕТИНОВОГО ПРОИЗВОДНОГО ТЕТРАГИДРОБЕНЗТИОФЕНА-3-КАРБОКСАМИДА, НА НЕКОТОРЫЕ ПОКАЗАТЕЛИ ЛИПИДНОГО ОБМЕНА У ЗДОРОВЫХ КРЫС И В УСЛОВИЯХ ЭКСПЕРИМЕНТАЛЬНОЙ ГИПЕРЛИПИДЕМИИ

According to WHO data, cardiovascular diseases occupy a leading position in terms of the number per share of the population, both in Russia and in other countries. A prerequisite for the development of these pathologies is atherosclerosis. It is now recognized that drug therapy is leading in curbing the development of atherosclerosis and subsequent complications. In this regard, the urgency of the search for new lipid-lowering drugs aimed at the treatment of this disease is increasing. Recent studies have shown the promise of using the benzothiophene backbone for the synthesis of new effective drugs, since this core has various biological and pharmacological activities, which makes it possible to obtain effective antimicrobial, anticancer, anti-inflammatory, antioxidant, anti-tuberculosis, antidiabetic, anticonvulsant and other drugs on its basis.The purpose of this study was to study the lipid-lowering effect of the azomethine derivative 2-amino-4,5,6,7-tetrahydro-1-benzothiophene-3-carboxamide, a substance under the laboratory code BF-10, on some indicators of lipid metabolism in healthy rats and under pathological conditions with experimental hyperlipidemia. Atorvastatin was chosen as the reference drug. Determination of biochemical parameters of lipid metabolism in the blood serum and in the liver homogenate (the content of cholesterol, triglycerides, total lipids, LDL, VLDL and HDL) was determined by unified biochemical methods using standard Olvex Diagnosticum kits on a Dixion Torus 120 analyzer. Based on the analysis of the obtained data on the effect of the BF-10 substance on lipid metabolism, it can be concluded that they are comparable with the action of the highly effective reference drug atorvastatin, which allows us to expand information on the spectrum of biological activity of azomethine derivatives and consider the compound under the laboratory code BF-10 promising for further development.

New Chalcone-Triazole Hybrids with Promising Antimicrobial Activity in Multidrug Resistance Strains.

Resistance to antibiotics is an emerging problem worldwide, which leads to an increase in morbidity and mortality rates. Several mechanisms are attributed to bacterial resistance, overexpression of efflux pumps being one of the most prominent. As an attempt to develop new effective antimicrobial drugs, which could be able to act against resistant bacterial strains and considering the antimicrobial potential of flavonoids and triazolyl flavonoid derivatives, in particular chalcones, a small library of chalcone derivatives was synthesized and evaluated for its potential to act as antimicrobials and/or adjuvants in combination with antibiotics towards resistant bacteria. Although only compound 7 was able to act as antibacterial, compounds 1, 2, 4, 5, 7, and 9 revealed to be able to potentiate the activity of antibiotics in resistant bacteria. Moreover, five compounds (3, 5-8) demonstrated to be effective inhibitors of efflux pumps in Salmonella enterica serovar Typhimurium SL1344, and four compounds (1, 3, 7, and 10) showed higher ability than reserpine to inhibit biofilm formation of resistant Staphylococcus aureus 272123. Together, our results showed the potential of these compounds regarding reversion of bacterial resistance.