scholarly journals Synthesis, in vitro Antimicrobial Activity, and Docking Studies of some Pyrano[2,3-c] Pyrazole Derivatives

2021 ◽  
Vol 12 (4) ◽  
pp. 4705-4730
Keyword(s):  
In Silico ◽  
Public Health Problem ◽  
Multidrug Resistant ◽  
Docking Studies ◽  
Hospital Environment ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Drug Resistant Bacteria ◽  
Microbiological Methods

The hospital environment favors the circulation of drug-resistant bacteria. The researcher has oriented this public health problem to find an ideal tool for better patient management. Therefore, this study aims to assess the biological activity of some synthetic molecules against multidrug-resistant bacterial isolates from patients suspected of nosocomial infections. After synthesizing and characterizing five targeted compounds 5(a-e), a sensitivity test is carried out to screen their antibacterial activity via microbiological methods (diffusion and microdilution). The forgoing results confirmed that (5c) compound has better potential against all studied strains with a minimum inhibitory concentration (MIC) that varies between 6.25 - 50 mg/mL. The lowest MIC values were observed with Klebsiella pneumonia, while the greatest value of the same parameter was obtained with L. monocytogenes. On the other side, in silico pharmacological studies like ADME and docking data were implemented for the selected compounds 5(a-e) to comprehensively understand the plausible mode of interaction with the target. Docking results indicated that the compounds 5c and 5b have considerable binding energy towards the active site of Escherichia coli MurB and S. aureus DNA gyrase B. In vitro and in silico data have confirmed the antimicrobial potentials of the five synthetic compounds; this data can be added and supported the literature on the bioactivity of pyrano[2,3-c] pyrazole.

scholarly journals Thermo-responsive triple-function nanotransporter for efficient chemo-photothermal therapy of multidrug-resistant bacterial infection

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Guangchao Qing ◽  
Xianxian Zhao ◽  
Ningqiang Gong ◽  
Jing Chen ◽  
Xianlei Li ◽  
...  
Keyword(s):  
Near Infrared ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Limited Effect ◽  
Bacterial Membranes ◽  
Change Mechanism ◽  
Drug Resistant Bacteria ◽  
New Strategies

Abstract New strategies with high antimicrobial efficacy against multidrug-resistant bacteria are urgently desired. Herein, we describe a smart triple-functional nanostructure, namely TRIDENT (Thermo-Responsive-Inspired Drug-Delivery Nano-Transporter), for reliable bacterial eradication. The robust antibacterial effectiveness is attributed to the integrated fluorescence monitoring and synergistic chemo-photothermal killing. We notice that temperature rises generated by near-infrared irradiation did not only melt the nanotransporter via a phase change mechanism, but also irreversibly damaged bacterial membranes to facilitate imipenem permeation, thus interfering with cell wall biosynthesis and eventually leading to rapid bacterial death. Both in vitro and in vivo evidence demonstrate that even low doses of imipenem-encapsulated TRIDENT could eradicate clinical methicillin-resistant Staphylococcus aureus, whereas imipenem alone had limited effect. Due to rapid recovery of infected sites and good biosafety we envision a universal antimicrobial platform to fight against multidrug-resistant or extremely drug-resistant bacteria.

Bioactivity guided extraction of PDHC [3,3’-(propane-2,2-diyl)bis(3,4,5,6,7,8- hexahydro-1h-isochromene)]: A Novel antibacterial compound from an ornamental plant Polyalthia longifolia

2021 ◽  
pp. 2101-2107
Author(s):  
Gayathri Segaran ◽  
Lokesh Ravi ◽  
Mythili Sathiavelu
Keyword(s):  
Antibacterial Activity ◽  
In Silico ◽  
Antibacterial Effect ◽  
Docking Studies ◽  
Trna Synthetase ◽  
Resistant Bacteria ◽  
In Silico Docking ◽  
Antibacterial Assay ◽  
Polyalthia Longifolia

Objective: The objective of the study was to determine and compare the antibacterial effect of different ornamental plants and to isolate the effective bioactive compound with antibacterial activity from Polyalthia longifolia. Methods: Petroleum ether and methanol extracts of Bougainvillea glabra, Polyalthia longifolia, Ixora coccinea Linn. ,Plumeria rubra and Euphorbia milli leaves were investigated for antimicrobial activity by performing agar well difusion method. The plant extract with the highest antibacterial activity was selected and further used for the isolation of antibacterial compounds. In silico docking studies and in vitro antibacterial assay was performed to analyze the biological activity of pure compound. Results: The highest antibacterial activity was found in the pet ether of Polyalthia longifolia against all the tested bacterial strains and the extract was further selected for compound separation. A novel compound 3,3’-(propane-2,2-diyl)bis(3,4,5,6,7,8-hexahydro-1H-isochromene) (PHDC) with a molecular weight of 316.35 g/mol and molecular formula C21H32O2 was identified from Polyalthia longifolia by using spectroscopic studies. In the in vitro antibacterial assay, PHDC demonstrated significant antibacterial showed against Protease mirabilis. In silico docking studies revealed that PHDC showed antibacterial activity by inhibiting tRNA Synthetase (IleRS). PHDC exhibited the lowest binding energy of - 8.7Kcal/Mol for Isoleucyl tRNA Synthetase (IleRS), the protein responsible for protein synthesis. Conclusion: The emergence of multiple antibiotics resistant microbes has become huge nowadays and the infections caused by these resistant microbes cannot be treated with antibiotics. PHDC is a novel compound extracted from Polyalthia longifolia showed significant antibacterial effect and we suggest that the compound can be further used as lead molecules to overcome the infections caused by antibiotic resistant bacteria.

Tea: An anti-bacterial agent against drug resistant bacteria

2021 ◽  
Vol 15 (10) ◽  
pp. 2506-2511
Author(s):  
Nayyab Sultan ◽  
Sabahat Javaid Butt ◽  
Wajeeha Mehak ◽  
Samreen Qureshi ◽  
Syed Hamza Abbas ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Salmonella Typhi ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Drug Resistant ◽  
Antibiotic Resistant ◽  
Bacterial Agent ◽  
Drug Resistant Bacteria ◽  
Scientific World

Antibiotics have played a crucial role in the treatment of bacterial infections. Past few decades are marked with advancement of multidrug resistant (MDR) pathogens, which have endangered antibiotic’s therapeutic efficacy. Scientific world is now struggling with the crisis of MDR pathogens. This supreme matter demands careful attention or otherwise it would jeopardize clinical management of infectious diseases. Implication of alternative approaches can pave a new way in the treatment of these troublesome bacteria. Tea leaves are known to pose antibacterial activity against many pathogenic microorganisms. This review has summarized the antibacterial potential of tea leave’s extracts against resistant bacterial pathogens such as Staphylococcus aureus, Pseudomonas aeruginosa, Helicobacter pylori, Escherichia coli, Klebsiella pneumonia, Salmonella typhi, Acenitobacter spp, Campylobacter spp. Consumption of natural products such as tea may very well replace, minimize or obliterate this complicated situation. Keywords: Anti-bacterial, Tea, Camellia sinensis, Drug resistant bacteria, Antibiotic resistant bacteria, Synergism, Polyphenols.

scholarly journals Survival of antibacterial resistance microbes in hospital-generated recycled wastewater

2016 ◽  
Vol 14 (6) ◽  
pp. 942-949 ◽  
Author(s):  
Kumarasingam Kalaiselvi ◽  
Vincent Mangayarkarasi ◽  
Doraisami Balakrishnan ◽  
Vasudevan Chitraleka
Keyword(s):  
Pathogenic Bacteria ◽  
Tertiary Care ◽  
Hospital Environment ◽  
Effluent Treatment ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Hospital Wastewater ◽  
Recycled Water ◽  
Drug Resistant Bacteria ◽  
Wastewater Samples

Hospital wastewater has the potential to be a threat to the hospital environment as it can contain pathogenic bacteria that may facilitate the resistant nature of organisms within effluent or water treatment plants. The recycling of hospital wastewater should have good quality. This study was carried out to highlight the incidence of antibiotic resistant bacteria in hospital-generated recycled water. This study was conducted in a tertiary care teaching hospital during June 2013–June 2014. One hundred and forty wastewater samples were aseptically collected at different stages in the recycling plant. The samples were processed within 2 hours following standard procedures for identification of bacteria and the pathogenic bacteria were isolated. The mostly identified pathogens were Staphylococcus aureus (11.42%), Pseudomonas aeruginosa (9.28%), Enterococcus faecalis (10%) and Bacillus subtilis (8.57%) which were removed by treatment, but Escherichia coli (16.42%), Klebsiella pneumonia (8.57%), and Proteus mirabilis (11.42%) survived in the final sedimentation tank (lagoon) from where this water will be used for gardening purposes. An antibiogram study showed these pathogens were resistant to first-line antibiotics. Effluent treatment plants in hospitals should be monitored for the fulfillment of the guidelines and quality control of treated water to stop the emergence of multi-drug resistant bacteria in the hospital environment.

scholarly journals In vitro and in vivo toxicity and antibacterial efficacy of melittin against clinical extensively drug-resistant bacteria

2021 ◽  
Vol 22 (1) ◽  
Author(s):  
Parvin Askari ◽  
Mohammad Hasan Namaei ◽  
Kiarash Ghazvini ◽  
Mehran Hosseini
Keyword(s):  
Lethal Dose ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Antibacterial Efficacy ◽  
Drug Resistant ◽  
Extensively Drug Resistant ◽  
Drug Resistant Bacteria ◽  
Antimicrobial Evaluation

Abstract Background Melittin is one of the most studied antimicrobial peptides, and several in vitro experiments have demonstrated its antibacterial efficacy. However, there is evidence showing melittin has non-promising effects such as cytotoxicity and hemolysis. Therefore, concerns about unwanted collateral toxicity of melittin lie ahead in the path toward its clinical development. With these considerations, the present study aimed to fill the gap between in vitro and in vivo studies. Methods In the first step, in vitro toxicity profile of melittin was assessed using cytotoxicity and hemolysis tests. Next, a maximum intraperitoneal (i.p.) sub-lethal dose was determined using BALB/c mice. Besides toxicity, antimicrobial efficacy of melittin against extensively drug-resistant (XDR) Acinetobacter baumannii, methicillin-resistant Staphylococcus aureus (MRSA), and KPC-producing Klebsiella pneumonia (KPC-KP) pathogens were tested using both in vitro and in vivo methods. Results Melittin showed extensive hemolysis (HD50 = 0.44 µg/mL), and cytotoxicity (IC50 = 6.45 µg/mL) activities with i.p. LD50 value of 4.98 mg/kg in BALB/c mice. In vitro antimicrobial evaluation showed melittin MIC range from 8 to 32 µg/mL for the studied pathogens. Treatment of infected mice with repeated sub-lethal doses of melittin (2.4 mg/kg) displayed no beneficial effect on their survival and peritoneal bacterial loads. Conclusions These results indicate that melittin at its safe dose could not exhibit antimicrobial activity, which hinders its application in clinical practice.

scholarly journals AMPing up the search: An in silico approach to identifying Antimicrobial Peptides (AMPs) with potential anti-biofilm activity

2021 ◽  
Author(s):  
Shreeya Mhade ◽  
Stutee Panse ◽  
Gandhar Tendulkar ◽  
Rohit Awate ◽  
Snehal Kadam ◽  
...  
Keyword(s):  
Antimicrobial Peptides ◽  
In Silico ◽  
Biofilm Formation ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
C Protein ◽  
Pilus Biogenesis ◽  
Natural And Synthetic

AbstractAntibiotic resistance is a public health threat, and the rise of multidrug-resistant bacteria, including those that form protective biofilms, further compounds this challenge. Antimicrobial peptides (AMPs) have been recognized for their anti-infective properties, including their ability to target processes important for biofilm formation. However, given the vast array of natural and synthetic AMPs, determining potential candidates for anti-biofilm testing is a significant challenge. In this study, we present an in silico approach, based on open-source tools, to identify AMPs with potential anti-biofilm activity. This approach is developed using the sortase-pilin machinery, important for adhesion and biofilm formation, of the multidrug-resistant, biofilm-forming pathogen C. striatum as the target. Using homology modeling, we modeled the structure of the C. striatum sortase C protein, resembling the semi-open lid conformation adopted during pilus biogenesis. Next, we developed a structural library of 5544 natural and synthetic AMPs from sequences in the DRAMP database. From this library, AMPs with known anti-Gram positive activity were filtered, and 100 select AMPs were evaluated for their ability to interact with the sortase C protein using in-silico molecular docking. Based on interacting residues and docking scores, we built a preference scale to categorize candidate AMPs in order of priority for future in vitro and in vivo biofilm studies. The considerations and challenges of our approach, and the resources developed, which includes a search-enabled repository of predicted AMP structures and protein-peptide interaction models relevant to biofilm studies (B-AMP), can be leveraged for similar investigations across other biofilm targets and biofilm-forming pathogens.

scholarly journals Current Mechanism of Bacterial Resistance to Antimicrobials

2018 ◽  
Vol 10 (01) ◽  
pp. 55-64
Author(s):  
Sonali Gangwar ◽  
Keerti Kaushik ◽  
Maya Datt Joshi
Keyword(s):  
Molecular Mechanisms ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
Multidrug Resistant ◽  
Hospital Environment ◽  
Health Concern ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Pathogenic Variants ◽  
Drug Resistant Bacteria

Serious infectious diseases are caused by bacterial pathogens that represents a serious public health concern. Antimicrobial agents are indicated for the treatment bacterial infections.Various bacteria carries several resistance genes also called multidrug resistant (MDR). Multidrug resistant organisms have emerged not only in the hospital environment but are now often identified in community settings, suggesting the reservoirs of antibiotic resistant bacteria are present outside the hospital. Drug resistant bacteria that are selected with a single drug are also frequently multi-drug resistant against multiple structurally different drugs, thus confounding the chemotherapeutic efficacy of infectious disease caused by such pathogenic variants. The molecular mechanisms by which bacteria have common resistance to antibiotics are diverse and complex. This review highlights the mechanism of bacterial resistance to antimicrobials.

scholarly journals Random Mutagenesis of theAspergillus oryzaeGenome Results in Fungal Antibacterial Activity

2013 ◽  
Vol 2013 ◽  
pp. 1-5 ◽  
Author(s):  
Cory A. Leonard ◽  
Stacy D. Brown ◽  
J. Russell Hayman
Keyword(s):  
Staphylococcus Aureus ◽  
Antibacterial Activity ◽  
Random Mutagenesis ◽  
Multidrug Resistant ◽  
New Drugs ◽  
Resistant Bacteria ◽  
Klebsiella Pneumonia ◽  
Antibacterial Compounds ◽  
Severe Infections

Multidrug-resistant bacteria cause severe infections in hospitals and communities. Development of new drugs to combat resistant microorganisms is needed. Natural products of microbial origin are the source of most currently available antibiotics. We hypothesized that random mutagenesis ofAspergillus oryzaewould result in secretion of antibacterial compounds. To address this hypothesis, we developed a screen to identify individualA. oryzaemutants that inhibit the growth of Methicillin-resistantStaphylococcus aureus(MRSA)in vitro. To randomly generateA. oryzaemutant strains, spores were treated with ethyl methanesulfonate (EMS). Over 3000 EMS-treatedA. oryzaecultures were tested in the screen, and one isolate, CAL220, exhibited altered morphology and antibacterial activity. Culture supernatant from this isolate showed antibacterial activity against Methicillin-sensitiveStaphylococcus aureus, MRSA, andPseudomonas aeruginosa, but notKlebsiella pneumoniaorProteus vulgaris. The results of this study support our hypothesis and suggest that the screen used is sufficient and appropriate to detect secreted antibacterial fungal compounds resulting from mutagenesis ofA. oryzae. Because the genome ofA. oryzaehas been sequenced and systems are available for genetic transformation of this organism, targeted as well as random mutations may be introduced to facilitate the discovery of novel antibacterial compounds using this system.

scholarly journals Histatin-Derived Monomeric and Dimeric Synthetic Peptides Show Strong Bactericidal Activity towards Multidrug-Resistant Staphylococcus aureus In Vivo

2007 ◽  
Vol 51 (9) ◽  
pp. 3416-3419 ◽  
Author(s):  
Mick M. Welling ◽  
Carlo P. J. M. Brouwer ◽  
Wim van ′t Hof ◽  
Enno C. I. Veerman ◽  
Arie V. Nieuw Amerongen
Keyword(s):  
Staphylococcus Aureus ◽  
Soft Tissue ◽  
Bactericidal Activity ◽  
Synthetic Peptides ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Drug Resistant Bacteria

ABSTRACT Homodimerization of histatin-derived peptides generally led to improved bactericidal activity against Staphylococcus aureus in vitro. In vivo, monomers and dimers were equally active in killing bacteria in mice with a soft tissue infection. Altogether, these peptides are promising compounds for the development of novel therapeutics against infections with drug-resistant bacteria.

Prospecting Potential Inhibitors of Sortase A from Enterococcus faecalis: A Multidrug Resistant Bacteria, through In-silico and In-vitro Approaches

2020 ◽  
Vol 27 (7) ◽  
pp. 582-592
Author(s):  
Satyajeet Das ◽  
Vijay Kumar H.S. ◽  
Sudhir K. Pal ◽  
Vijay K. Srivastava ◽  
Anupam Jyoti ◽  
...  
Keyword(s):  
Enterococcus Faecalis ◽  
In Silico ◽  
Multidrug Resistant ◽  
Resistant Bacteria ◽  
Sortase A ◽  
In Silico Docking ◽  
In Vitro Binding ◽  
Vitro Binding ◽  
Potential Inhibitors

Background: Enterococcus faecalis (Ef) infections are becoming dreadfully common in hospital environments. Infections caused by Ef are difficult to treat because of its acquired resistance to different class of antibiotics, making it a multidrug resistant bacteria. Key pathogenic factor of Ef includes its ability to form biofilm on the surface of diagnostic and other medical devices. Sortase A (SrtA) is a cysteine transpeptidase which plays a pivotal role in the formation of biofilm in Ef, hence, it is considered as an important enzyme for the pathogenesis of Ef. Thus, inhibition of (SrtA) will affect biofilm formation, which will reduce its virulence and eventually Ef infection will be abridged. Objective: To find potential inhibitors of Enterococcus faecalis Sortase A (EfSrtA) through insilico and in-vitro methods. Methods: Gene coding for EfSrtA was cloned, expressed and purified. Three-dimensional model of EfSrtA was created using Swiss-Model workspace. In-silico docking studies using Autodock vina and molecular dynamics simulations of the modelled structures using Gromacs platform were performed to explore potential lead compounds against EfSrtA. In-vitro binding experiments using spectrofluorometric technique was carried out to confirm and validate the study. Results: In-silico docking and in-vitro binding experiments revealed that curcumin, berberine and myricetin bound to EfSrtA at nanomolar concentrations with high affinity. Conclusion: This is a first structural report of EfSrtA with curcumin, berberine and myricetin. Taking in account the herbal nature of these compounds, the use of these compounds as inhibitors will be advantageous. This study validated curcumin, berberine and myricetin as potential inhibitors of EfSrtA.

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