scholarly journals Silver i-motifs and their antibacterial activity

2021 ◽  
Author(s):  
Jessica Bratt
Keyword(s):  
Antibacterial Activity ◽  
Therapeutic Potential ◽  
Bacterial Load ◽  
Therapeutic Benefit ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Drug Resistant Bacteria ◽  
Low Concentrations

<p>The spread of antibiotic resistance and the emergence of multi-drug resistant bacteria is a major threat to public health. This study investigated a unique cytosine rich DNA structure, the i-Motif to deliver soluble Ag+ as a novel antimicrobial agent (AgiMs). AgiMs were evaluated in vitro against P. aeruginosa and A. baumannii strains. AgiMs displayed significant antibacterial activity against both P. aeruginosa and A. baumannii (median MIC: 0.875 µM and 0.75 µM, respectively) by rapid, bactericidal and concentration-dependent effect. Low concentrations of AgiMs showed efficacy against PAO1 20-h biofilms, resulting in 57% reduction in biomass (5 x MIC). A single dose of AgiMs extended survival of G. Mellonella larvae, with the therapeutic benefit paralleled in the reduction of internal bacterial load. Synergistic interactions were observed with the combination of AgiMs and tobramycin, a common antibiotic used to treat P. aeruginosa infections; indicating the potential for AgiMs to reinstate the potency of current antibiotics. This silver-based agent might be an alternative to the failing antibiotic regimes for MDR resistant infections. Further in vitro and in vivo studies are warranted to confirm the therapeutic potential. </p>

scholarly journals Silver i-motifs and their antibacterial activity

2021 ◽  
Author(s):  
Jessica Bratt
Keyword(s):  
Antibacterial Activity ◽  
Therapeutic Potential ◽  
Bacterial Load ◽  
Therapeutic Benefit ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Drug Resistant Bacteria ◽  
Low Concentrations

<p>The spread of antibiotic resistance and the emergence of multi-drug resistant bacteria is a major threat to public health. This study investigated a unique cytosine rich DNA structure, the i-Motif to deliver soluble Ag+ as a novel antimicrobial agent (AgiMs). AgiMs were evaluated in vitro against P. aeruginosa and A. baumannii strains. AgiMs displayed significant antibacterial activity against both P. aeruginosa and A. baumannii (median MIC: 0.875 µM and 0.75 µM, respectively) by rapid, bactericidal and concentration-dependent effect. Low concentrations of AgiMs showed efficacy against PAO1 20-h biofilms, resulting in 57% reduction in biomass (5 x MIC). A single dose of AgiMs extended survival of G. Mellonella larvae, with the therapeutic benefit paralleled in the reduction of internal bacterial load. Synergistic interactions were observed with the combination of AgiMs and tobramycin, a common antibiotic used to treat P. aeruginosa infections; indicating the potential for AgiMs to reinstate the potency of current antibiotics. This silver-based agent might be an alternative to the failing antibiotic regimes for MDR resistant infections. Further in vitro and in vivo studies are warranted to confirm the therapeutic potential. </p>

scholarly journals Developing an antibiotic effective against multi-drug resistant bacteria.

2014 ◽  
Vol 70 (a1) ◽  
pp. C714-C714
Author(s):  
Calvin Steussy ◽  
Cynthia Stauffacher ◽  
Mark Lipton ◽  
Mohamed Seleem
Keyword(s):  
Pathogenic Bacteria ◽  
Modern Medicine ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Lead Compound ◽  
Drug Resistant Bacteria ◽  
Coa Reductase

The emergence of multi-drug resistant pathogenic bacteria is one of the great challenges to modern medicine. The gram positive cocci Methicillin Resistant Staphylococcus aureus (MRSA) and Vancomycin Resistant Enterococcus faecalis (VRE) are two particularly virulent examples. In vivo studies have shown that the eukaryotic like 'mevalonate' isoprenoid pathway used by these pathogenic cocci is essential to their growth and virulence [1]. Our structures of HMG-CoA reductase (HMGR) from P. mevalonii demonstrated that the bacterial enzymes are structurally distinct from the human enzymes allowing for specific antibacterial activity [2]. High throughput in vitro screening against bacterial HMGR at the Southern Research Center, Birmingham, AL uncovered a lead compound with an IC50 of 80 µM with a competitive mode of action. Our x-ray crystal structures of HMGR from E. faecalis complexed with the lead compound and its variations have informed the synthesis of new inhibitors that have improved the IC50 to 5 µM [3]. Studies of this compound show it to be active against both MRSA and VRE in culture, effective against these bacteria in biofilms, and efficacious in a model system of eukaryotic infection. Structures and kinetics of these compounds will be presented and future directions discussed.

scholarly journals Thanatin: An Emerging Host Defense Antimicrobial Peptide with Multiple Modes of Action

2021 ◽  
Vol 22 (4) ◽  
pp. 1522
Author(s):  
Rachita Dash ◽  
Surajit Bhattacharjya
Keyword(s):  
Therapeutic Potential ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Multiple Modes ◽  
Modes Of Action ◽  
Drug Resistant Bacteria ◽  
Low Concentrations ◽  
Spectrum Activity ◽  
Bacteria And Fungi

Antimicrobial peptides (AMPs) possess great potential for combating drug-resistant bacteria. Thanatin is a pathogen-inducible single-disulfide-bond-containing β-hairpin AMP which was first isolated from the insect Podisus maculiventris. The 21-residue-long thanatin displays broad-spectrum activity against both Gram-negative and Gram-positive bacteria as well as against various species of fungi. Remarkably, thanatin was found to be highly potent in inhibiting the growth of bacteria and fungi at considerably low concentrations. Although thanatin was isolated around 25 years ago, only recently has there been a pronounced interest in understanding its mode of action and activity against drug-resistant bacteria. In this review, multiple modes of action of thanatin in killing bacteria and in vivo activity, therapeutic potential are discussed. This promising AMP requires further research for the development of novel molecules for the treatment of infections caused by drug resistant pathogens.

Medicinal Plants and Bioactive Compounds for Diabetes Management: Important Advances for Drug Discovery

2020 ◽  
Vol 26 ◽  
Author(s):  
Kondeti Ramudu Shanmugam ◽  
Bhasha Shanmugam ◽  
Gangigunta Venkatasubbaiah ◽  
Sahukari Ravi ◽  
Kesireddy Sathyavelu Reddy
Keyword(s):  
Herbal Medicine ◽  
Medicinal Plants ◽  
Bioactive Compounds ◽  
Diabetes Management ◽  
Therapeutic Potential ◽  
Public Health Problem ◽  
In Vivo Studies ◽  
Major Public Health Problem

Background : Diabetes is a major public health problem in the world. It affects each and every part of the human body and also leads to organ failure. Hence, great progress made in the field of herbal medicine and diabetic research. Objectives: Our review will focus on the effect of bioactive compounds of medicinal plants which are used to treat diabetes in India and other countries. Methods: Information regarding diabetes, oxidative stress, medicinal plants and bioactive compounds were collected from different search engines like Science direct, Springer, Wiley online library, Taylor and francis, Bentham Science, Pubmed and Google scholar. Data was analyzed and summarized in the review. Results and Conclusion: Anti-diabetic drugs that are in use have many side effects on vital organs like heart, liver, kidney and brain. There is an urgent need for alternative medicine to treat diabetes and their disorders. In India and other countries herbal medicine was used to treat diabetes. Many herbal plants have antidiabetic effects. The plants like ginger, phyllanthus, curcumin, aswagandha, aloe, hibiscus and curcuma showed significant anti-hyperglycemic activities in experimental models and humans. The bioactive compounds like Allicin, azadirachtin, cajanin, curcumin, querceitin, gingerol possesses anti-diabetic, antioxidant and other pharmacological properties. This review focuses on the role of bioactive compounds of medicinal plants in prevention and management of diabetes. Conclusion: Moreover, our review suggests that bioactive compounds have the potential therapeutic potential against diabetes. However, further in vitro and in vivo studies are needed to validate these findings.

Effects of Probiotics in the Management of Infected Chronic Wounds: From Cell Culture to Human Studies

2020 ◽  
Vol 15 (3) ◽  
pp. 193-206
Author(s):  
Brognara Lorenzo ◽  
Salmaso Luca ◽  
Mazzotti Antonio ◽  
Di M. Alberto ◽  
Faldini Cesare ◽  
...  
Keyword(s):  
Chronic Wounds ◽  
Animal Experiments ◽  
Multidrug Resistant ◽  
Preliminary Evidence ◽  
Human Studies ◽  
In Vivo Studies ◽  
Resistant Bacteria ◽  
Keywords Probiotics

Background: Chronic wounds are commonly associated with polymicrobial biofilm infections. In the last years, the extensive use of antibiotics has generated several antibiotic-resistant variants. To overcome this issue, alternative natural treatments have been proposed, including the use of microorganisms like probiotics. The aim of this manuscript was to review current literature concerning the application of probiotics for the treatment of infected chronic wounds. Methods: Relevant articles were searched in the Medline database using PubMed and Scholar, using the keywords “probiotics” and “wound” and “injuries”, “probiotics” and “wound” and “ulcer”, “biofilm” and “probiotics” and “wound”, “biofilm” and “ulcer” and “probiotics”, “biofilm” and “ulcer” and “probiotics”, “probiotics” and “wound”. Results: The research initially included 253 articles. After removal of duplicate studies, and selection according to specific inclusion and exclusion criteria, 19 research articles were included and reviewed, accounting for 12 in vitro, 8 in vivo studies and 2 human studies (three articles dealing with animal experiments included also in vitro testing). Most of the published studies about the effects of probiotics for the treatment of infected chronic wounds reported a partial inhibition of microbial growth, biofilm formation and quorum sensing. Discussion: The application of probiotics represents an intriguing option in the treatment of infected chronic wounds with multidrug-resistant bacteria; however, current results are difficult to compare due to the heterogeneity in methodology, laboratory techniques, and applied clinical protocols. Lactobacillus plantarum currently represents the most studied strain, showing a positive application in burns compared to guideline treatments, and an additional mean in chronic wound infections. Conclusions: Although preliminary evidence supports the use of specific strains of probiotics in certain clinical settings such as infected chronic wounds, large, long-term clinical trials are still lacking, and further research is needed.

scholarly journals The Multifunctional Sactipeptide Ruminococcin C1 Displays Potent Antibacterial Activity In Vivo as Well as Other Beneficial Properties for Human Health

2021 ◽  
Vol 22 (6) ◽  
pp. 3253
Author(s):  
Clarisse Roblin ◽  
Steve Chiumento ◽  
Cédric Jacqueline ◽  
Eric Pinloche ◽  
Cendrine Nicoletti ◽  
...  
Keyword(s):  
Antibacterial Activity ◽  
Human Health ◽  
Biological Activities ◽  
Resistant Bacteria ◽  
Modified Peptides ◽  
The 1960S ◽  
Conventional Antibiotics ◽  
Clinical Potential

The world is on the verge of a major antibiotic crisis as the emergence of resistant bacteria is increasing, and very few novel molecules have been discovered since the 1960s. In this context, scientists have been exploring alternatives to conventional antibiotics, such as ribosomally synthesized and post-translationally modified peptides (RiPPs). Interestingly, the highly potent in vitro antibacterial activity and safety of ruminococcin C1, a recently discovered RiPP belonging to the sactipeptide subclass, has been demonstrated. The present results show that ruminococcin C1 is efficient at curing infection and at protecting challenged mice from Clostridium perfringens with a lower dose than the conventional antibiotic vancomycin. Moreover, antimicrobial peptide (AMP) is also effective against this pathogen in the complex microbial community of the gut environment, with a selective impact on a few bacterial genera, while maintaining a global homeostasis of the microbiome. In addition, ruminococcin C1 exhibits other biological activities that could be beneficial for human health, as well as other fields of applications. Overall, this study, by using an in vivo infection approach, confirms the antimicrobial clinical potential and highlights the multiple functional properties of ruminococcin C1, thus extending its therapeutic interest.

scholarly journals The Challenging Melanoma Landscape: From Early Drug Discovery to Clinical Approval

Cells ◽  
2021 ◽  
Vol 10 (11) ◽  
pp. 3088
Author(s):  
Mariana Matias ◽  
Jacinta O. Pinho ◽  
Maria João Penetra ◽  
Gonçalo Campos ◽  
Catarina Pinto Reis ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Drug Evaluation ◽  
Three Dimensional ◽  
Experimental Models ◽  
In Vivo Studies ◽  
Murine Models ◽  
In Vivo Experiments ◽  
Novel Therapeutic Strategies

Melanoma is recognized as the most dangerous type of skin cancer, with high mortality and resistance to currently used treatments. To overcome the limitations of the available therapeutic options, the discovery and development of new, more effective, and safer therapies is required. In this review, the different research steps involved in the process of antimelanoma drug evaluation and selection are explored, including information regarding in silico, in vitro, and in vivo experiments, as well as clinical trial phases. Details are given about the most used cell lines and assays to perform both two- and three-dimensional in vitro screening of drug candidates towards melanoma. For in vivo studies, murine models are, undoubtedly, the most widely used for assessing the therapeutic potential of new compounds and to study the underlying mechanisms of action. Here, the main melanoma murine models are described as well as other animal species. A section is dedicated to ongoing clinical studies, demonstrating the wide interest and successful efforts devoted to melanoma therapy, in particular at advanced stages of the disease, and a final section includes some considerations regarding approval for marketing by regulatory agencies. Overall, considerable commitment is being directed to the continuous development of optimized experimental models, important for the understanding of melanoma biology and for the evaluation and validation of novel therapeutic strategies.

scholarly journals Quorum Sensing Inhibition in Chromobacterium violaceum, Antibacterial Activity and GC-MS Analysis of Centaurea praecox (Oliv. & Hiern) Extracts

2020 ◽  
Vol 9 (4) ◽  
pp. 1569-1577
Keyword(s):  
Antibacterial Activity ◽  
Quorum Sensing ◽  
Research Strategy ◽  
Chromobacterium Violaceum ◽  
Resistant Bacteria ◽  
Drug Resistant ◽  
Control Drug ◽  
Ms Analysis ◽  
Drug Resistant Bacteria

The quorum sensing (QS) mechanism has become a viable research strategy for the discovery of plant-derived anti-virulent agents to control drug-resistant bacteria. The increasing incidences of drug-resistant bacteria and the effort to curb it necessitate this study. We investigated the QS inhibitory potential of Centaurea praecox extracts on Chromobacterium violaceum (CV), antibacterial activity, and determination of chemical composition using GC-MS. C. praecox was subjected to sequential extraction using hexane (HEX), dichloromethane (DCM), ethyl acetate (EA), ethanol (ET), and aqueous (AQ) solvents. The extracts were subsequently evaluated for antibacterial activity using disc diffusion and QS violacein inhibition using spectrophotometry. The antibacterial effects of the extracts were moderate on gram-positive bacteria at 4 mg/mL in the order: HEX >EA >DCM >ET =AQ. However, the DCM extract demonstrated the most effective violacein inhibition of ≥80% at 0.3 mg/mL. QS violacein inhibitions were generally found to be concentration-dependent in the order: DCM >EA >HEX >ET =AQ with efficacies of ≥ 90% inhibition at ≥ 0.6 mg/mL. GC-MS analysis on the most potent DCM extract revealed N-vinylmethanimine, N-ethyl formamide, and propanamide among components identified. We concluded that C. praecox DCM extract contains bioactive chemicals as QS inhibitors and potential anti-virulent agents capable of combating the pathogenicity of drug-resistant bacteria in vivo.

scholarly journals Anti-Inflammatory Potential of Daturaolone from Datura innoxia Mill.: In Silico, In Vitro and In Vivo Studies

2021 ◽  
Vol 14 (12) ◽  
pp. 1248
Author(s):  
Muhammad Waleed Baig ◽  
Humaira Fatima ◽  
Nosheen Akhtar ◽  
Hidayat Hussain ◽  
Mohammad K. Okla ◽  
...  
Keyword(s):  
In Silico ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Metabolic Reaction ◽  
Datura Innoxia ◽  
In Vivo Models ◽  
Immobility Time ◽  
Anti Inflammatory

Exploration of leads with therapeutic potential in inflammatory disorders is worth pursuing. In line with this, the isolated natural compound daturaolone from Datura innoxia Mill. was evaluated for its anti-inflammatory potential using in silico, in vitro and in vivo models. Daturaolone follows Lipinski’s drug-likeliness rule with a score of 0.33. Absorption, distribution, metabolism, excretion and toxicity prediction show strong plasma protein binding; gastrointestinal absorption (Caco-2 cells permeability = 34.6 nm/s); no blood–brain barrier penetration; CYP1A2, CYP2C19 and CYP3A4 metabolism; a major metabolic reaction, being aliphatic hydroxylation; no hERG inhibition; and non-carcinogenicity. Predicted molecular targets were mainly inflammatory mediators. Molecular docking depicted H-bonding interaction with nuclear factor kappa beta subunit (NF-κB), cyclooxygenase-2, 5-lipoxygenase, phospholipase A2, serotonin transporter, dopamine receptor D1 and 5-hydroxy tryptamine. Its cytotoxicity (IC50) value in normal lymphocytes was >20 µg/mL as compared to cancer cells (Huh7.5; 17.32 ± 1.43 µg/mL). Daturaolone significantly inhibited NF-κB and nitric oxide production with IC50 values of 1.2 ± 0.8 and 4.51 ± 0.92 µg/mL, respectively. It significantly reduced inflammatory paw edema (81.73 ± 3.16%), heat-induced pain (89.47 ± 9.01% antinociception) and stress-induced depression (68 ± 9.22 s immobility time in tail suspension test). This work suggests a possible anti-inflammatory role of daturaolone; however, detailed mechanistic studies are still necessary to corroborate and extrapolate the findings.

scholarly journals Click Activated Protodrugs Against Cancer Increase the Therapeutic Potential of Chemotherapy through Local Capture and Activation

2020 ◽  
Author(s):  
Kui Wu ◽  
Nathan Yee ◽  
Sangeetha Srinivasan ◽  
Amir Mahmoodi ◽  
Michael Zakharian ◽  
...  
Keyword(s):  
Therapeutic Potential ◽  
Unmet Need ◽  
Sodium Hyaluronate ◽  
Maximum Tolerated Dose ◽  
The Body ◽  
In Vivo Studies ◽  
Tumor Biomarker ◽  
Tumor Site

<div> <div> <div> <p>A desired goal of targeted cancer treatments is to achieve high tumor specificity with minimal side effects. Despite recent advances, this remains difficult to achieve in practice as most approaches rely on biomarkers or physiological differences between malignant and healthy tissue, and thus benefit only a subset of patients in need of treatment. To address this unmet need, we introduced a Click Activated Protodrugs Against Cancer (CAPAC) platform that enables targeted activation of drugs at a specific site in the body, i.e., a tumor. In contrast to antibodies (mAbs, ADCs) and other targeted approaches, the mechanism of action is based on in vivo click chemistry, and is thus independent of tumor biomarker expression or factors such as enzymatic activity, pH, or oxygen levels. The platform consists of a tetrazine-modified sodium hyaluronate-based biopolymer injected at a tumor site, followed by one or more doses of a trans-cyclooctene (TCO)- modified cytotoxic protodrug with attenuated activity administered systemically. The protodrug is captured locally by the biopolymer through an inverse electron-demand Diels-Alder reaction between tetrazine and TCO, followed by conversion to the active drug directly at the tumor site, thereby overcoming the systemic limitations of conventional chemotherapy or the need for specific biomarkers of traditional targeted therapy. Here, TCO-modified protodrugs of four prominent cytotoxics (doxorubicin, paclitaxel, etoposide and gemcitabine) are used, highlighting the modularity of the CAPAC platform. In vitro evaluation of cytotoxicity, solubility, stability and activation rendered the protodrug of doxorubicin, SQP33, as the most promising candidate for in vivo studies. Studies in rodents show that a single injection of the tetrazine-modified biopolymer, SQL70, efficiently captures SQP33 protodrug doses given at 10.8-times the maximum tolerated dose of conventional doxorubicin with greatly reduced systemic toxicity. </p> </div> </div> </div>

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