scholarly journals Recent Advances in Iron Chelation and Gallium-Based Therapies for Antibiotic Resistant Bacterial Infections

2021 ◽  
Vol 22 (6) ◽  
pp. 2876
Author(s):  
Víctor Vinuesa ◽  
Michael J. McConnell
Keyword(s):  
Antimicrobial Activity ◽  
Bacterial Infections ◽  
Antimicrobial Agents ◽  
Bacterial Species ◽  
Iron Chelation ◽  
Iron Chelator ◽  
In Vivo Studies ◽  
Iron Chelators

Iron is essential for multiple bacterial processes and is thus required for host colonization and infection. The antimicrobial activity of multiple iron chelators and gallium-based therapies against different bacterial species has been characterized in preclinical studies. In this review, we provide a synthesis of studies characterizing the antimicrobial activity of the major classes of iron chelators (hydroxamates, aminocarboxylates and hydroxypyridinones) and gallium compounds. Special emphasis is placed on recent in-vitro and in-vivo studies with the novel iron chelator DIBI. Limitations associated with iron chelation and gallium-based therapies are presented, with emphasis on limitations of preclinical models, lack of understanding regarding mechanisms of action, and potential host toxicity. Collectively, these studies demonstrate potential for iron chelators and gallium to be used as antimicrobial agents, particularly in combination with existing antibiotics. Additional studies are needed in order to characterize the activity of these compounds under physiologic conditions and address potential limitations associated with their clinical use as antimicrobial agents.

scholarly journals Pharmacological iron-chelation as an assisted nutritional immunity strategy against Piscirickettsia salmonis infection

2020 ◽  
Vol 51 (1) ◽  
Author(s):  
Mario Caruffo ◽  
Dinka Mandakovic ◽  
Madelaine Mejías ◽  
Ignacio Chávez-Báez ◽  
Pablo Salgado ◽  
...  
Keyword(s):  
Bacterial Infections ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Host Cells ◽  
Bacterial Disease ◽  
Protective Capacity ◽  
Intracellular Iron ◽  
Piscirickettsia Salmonis

Abstract Salmonid Rickettsial Septicaemia (SRS), caused by Piscirickettsia salmonis, is a severe bacterial disease in the Chilean salmon farming industry. Vaccines and antibiotics are the current strategies to fight SRS; however, the high frequency of new epizootic events confirms the need to develop new strategies to combat this disease. An innovative opportunity is perturbing the host pathways used by the microorganisms to replicate inside host cells through host-directed antimicrobial drugs (HDAD). Iron is a critical nutrient for P. salmonis infection; hence, the use of iron-chelators becomes an excellent alternative to be used as HDAD. The aim of this work was to use the iron chelator Deferiprone (DFP) as HDAD to treat SRS. Here, we describe the protective effect of the iron chelator DFP over P. salmonis infections at non-antibiotic concentrations, in bacterial challenges both in vitro and in vivo. At the cellular level, our results indicate that DFP reduced the intracellular iron content by 33.1% and P. salmonis relative load during bacterial infections by 78%. These findings were recapitulated in fish, where DFP reduced the mortality of rainbow trout challenged with P. salmonis in 34.9% compared to the non-treated group. This is the first report of the protective capacity of an iron chelator against infection in fish, becoming a potential effective host-directed therapy for SRS and other animals against ferrophilic pathogens.

scholarly journals Antimicrobial Activity from Species Plectranthus amboinicus (Lour.) Spreng, a Review

2020 ◽  
pp. 1-14
Author(s):  
Juliane Maria dos Santos Silva ◽  
Jackson Roberto Guedes da Silva Almeida ◽  
Cristiane dos Santos Cerqueira Alves ◽  
Daniel Amando Nery ◽  
Livia Maria Oliveira Damasceno ◽  
...  
Keyword(s):  
Antimicrobial Activity ◽  
Pathogenic Bacteria ◽  
Antimicrobial Agents ◽  
Therapeutic Potential ◽  
In Vivo Studies ◽  
Synergistic Activity ◽  
Popular Medicine ◽  
Plectranthus Amboinicus

Introduction: Nowadays, several bacteria have acquired resistance to available antimicrobial agents making necessary the search for new therapeutic alternatives. Plectranthus amboinicus L. is a succulent and aromatic herb, popularly known as thick leaf mint, used in popular medicine for the treatment of colds, digestive diseases, asthma, headache and to fight pathogenic bacteria activity. In view the antimicrobial activity of P. amboinicus this study had as aim to review publications involving researches about antimicrobial activity of this species. Materials and Methods: For this, PubMed, Scopus, Science Direct and Scielo databases were consulted in November 2020 using the keywords Plectranthus amboinicus and antimicrobial activity. In vitro and/or in vivo studies on the antimicrobial activity of the species in the last 10 years were considered. Results: The main microorganisms evaluated were: Klebsiella pneumoniae, Mycobacterium tuberculosis, Staphylococcus aureus, Escherichia coli, Pseudomonas aeruginosa, and some Candida species. The essential oils had carvacrol, germacrene D, thymol and camphor as main constituents. Most studies evaluated the antimicrobial activity using broth dilution and agar diffusion methods. In most studies essential oil, extracts and/or isolated substances showed significant antimicrobial activity. Synergistic activity was also observed through association with antibiotics. Conclusion: P. amboinicus has therapeutic potential for antimicrobial treatments and can be an alternative to the treatment of resistant microorganisms and that further in vivo and clinical studies with the species are still needed.

scholarly journals EVALUATION OF POTENTIAL ANTIMICROBIAL ACTIVITY OF SYNTHETIC FLAVONOIDS

2021 ◽  
Vol 10 (1) ◽  
pp. 76-82
Author(s):  
Prabhulingayya S Bhixavatimath ◽  
Yasmeen Maniyar ◽  
Akram Naikawadi ◽  
Vijayakumar D
Keyword(s):  
Antimicrobial Activity ◽  
Antifungal Activity ◽  
Antimicrobial Agents ◽  
Oxidative Cyclization ◽  
In Vivo Studies ◽  
Diffusion Method ◽  
Flavonoid Compounds ◽  
Antibacterial And Antifungal

Introduction: In recent times, most of the currently available antimicrobial agents have developed resistance. Extensive pharmacological activities including bactericidal and bacteriostatic nature of flavonoids, made them as priority agents in this aspect of research study. Synthetic flavonoids such as hydroxy thiophen derivatives were considered to evaluate for antimicrobial activity in this study.   Objective: The present study involves the analysis for antimicrobial activity of thiophen substituted synthetic flavonoids. Methods: Claisen-Schmidt method of condensation fallowed by oxidative cyclization reactions from substituted hydroxyacetophenone with aromatic aldehydes were used to synthesize the various analogues of flavonoid compounds. Then these compounds after their FTIR, 1H NMR, MS spectral characterization and elemental analysis, were screened for in vitro antibacterial and antifungal activity by using disc diffusion method followed by determining their respective zone of inhibitions. Results: All the synthesized test flavonoid compounds exhibited the good antibacterial and antifungal  spectrum activity over B. subtilis, S. aureus, E. coli and P. aeurugenosa bacteria and Candida albicans and Aspergillus niger fungal microbes. However compounds such as F1, F2 and F4 showed moderately significant antibacterial activity against P. aerugenosa organism than the other test compounds and the same F1 and F2 test compounds exhibited significant antifungal activity at100µg concentration. Conclusion:  The present study demonstrated that the novel thiophen substituted flavonoids (F1, F2, F3 and F4 ) found to have promising antimicrobial and antifungal activity which needs to be confirmed by in vivo studies.

scholarly journals An experimental in-vitro study to evaluate the anti-helicobacter activity of Glycyrrhetinic acid

2019 ◽  
Vol 27 (1) ◽  
pp. 63-71 ◽  
Author(s):  
Muhammet Murat Celik ◽  
Nizami Duran
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
In Vitro Study ◽  
Glycyrrhetinic Acid ◽  
Test Method ◽  
In Vivo Studies ◽  
H Pylori ◽  
Mic Value

Abstract Aim: The aim of this study was to investigate the in-vitro efficacy of Glycyrrhetinic acid against Helicobacter pylori (H. pylori) strains, as compared with conventional antibacterial agents. Methods: A total of 41 H. pylori isolates were used, 6 of which were of standard strains (NCTC 1637), 8 of which were drug-sensitive, and 27 were resistant to drugs isolates. Clarithromycin and metronidazole resistance in all strains of H. pylori were determined by the Epsilometer test (E-test) method. MIC study was performed by using microdilution broth method. Results: Glycyrrhetinic acid was found to be effective against H. pylori NCTC 1637 in doses of 12.0±4.38 µg/mL, while the MIC value of clinical H. pylori isolates susceptible to antimicrobials was 20.8±10.11 µg/ml. It was found that the MIC values for antimicrobial-sensitive clinical H. pylori isolates was higher when compared with H. pylori NCTC 1637 strains. The MIC values of the standard antimicrobial agents against drug-resistant H. pylori strains were higher than H. pylori NCTC 1637 strains and drug-sensitive H. pylori strains. The MIC value was found to be 14.22±7.77 µg/ml for metronidazole, 3.89±1.90 µg/ml for clarithromycin, 2.33±1.0 µg/ml for amoxicillin, 2.44±0.88 µg/ml for levofloxacin and 4.89±2.47 µg/ml for tetracycline, whereas the MIC value of Glycyrrhetinic acid was 26.67±8.0 µg/ml in metronidazole-resistant H. pylori isolates. Besides, MIC values of the antimicrobials and 18ß-Glycyrrhetinic acid among the strains resistant to clarithromycin were as follows: 3.25±2.12 µg/ml for metronidazole, 9.71±4.54 µg/ml for clarithromycin, 2.06±1.32 µg/ml for amoxicillin, 3.88±4.22 µg/ml for levofloaxacin and 3.25±1.04 µg/mL for tetracycline and 22.0±11.11 µg/ml for Glycyrrhetinic acid. Conclusion: Glycyrrhetinic acid had significant antimicrobial activity against H. pylori strains. Although further in-vivo studies are needed on antimicrobial activity of Glycyrrhetinic acid, increased resistance to drugs currently used in treatment suggests that Glycyrrhetinic acid may be a potential agent for the treatment of H. pylori.

Synthesis of Novel 3(N,N-dialkylamino)alkyl/phenyl Substituted Thieno [2,3-d]pyrimidinones as H1-Anti-Histaminic and Antimicrobial Agents

2019 ◽  
Vol 15 (1) ◽  
pp. 63-70
Author(s):  
Shiv Dev Singh ◽  
Arvind Kumar ◽  
Firoz Babar ◽  
Neetu Sachan ◽  
Arun Kumar Sharma
Keyword(s):  
Antimicrobial Activity ◽  
Potassium Hydroxide ◽  
Antimicrobial Agents ◽  
Pyrimidine Ring ◽  
Antimicrobial Activities ◽  
Screening Methods ◽  
Chlorpheniramine Maleate ◽  
In Vivo Screening

Background: Thienopyrimidines are the bioisoster of quinazoline and unlike quinazoline exist in three isomeric forms corresponding to the three possible types annulation of thiophene to the pyrimidine ring viz thieno[2,3-d] pyrimidine, thieno[3,2-d] pyrimidine and thieno[3,4-d]pyrimidine. Heterocyclic containing the thienopyrimidinone moiety exhibits various pronounced activities such as anti-hypertensive, analgesic and anti-inflammatory, antiviral, platelet aggregation inhibitory, antiprotozoal bronchodilatory, phosphodiesterase inhibitory, antihistaminic, antipsychotic and antimicrobial activity. Objective: Synthesis of novel 3(N,N-dialkylamino)alkyl/phenyl substituted thieno[2,3-d]pyrimidinones as H1-anti-histaminic and antimicrobial agents. Methods: A series of 3-[(N,N-dialkylamino)alkyl/phenyl]-2-(1H)thioxo-5,6,7,8-tetrahydrobenzo(b) thieno(2,3-d)pyrimidine-4(3H)-ones[4a-d], their oxo analogous [5a-d] and 3-[(N,N-dialkylamino)alkyl]- 2-chlorophenyl-5,6,7,8-tetrahydrobenzo(b)thieno(2,3-d)pyrimidine- 4 (3H)-ones[6a-d]derivative were synthesized from 2-amino-4,5,6,7-tetrahydrobenzo(b)thiophene-3-carboxylic acid by nucleophilic substitution of different N,N-dialkyl alkylene/phenylene diamines on activated 3-acylchloride moiety followed by cyclocondensation with carbon disulfide and ethanolic potassium hydroxide to get [4a-d] and in second reaction by condensation with 4-chlorobenzoyl chloride to get [6a-d] by single pot novel innovative route. The oxo analogous [5a-d] were prepared by treating derivatives [4a-d] with potassium permagnate in ethanolic KOH. The synthesized compound were evaluated for H1-antihistaminic and antimicrobial activities. Results: All synthesized compounds exhibited significant H1-antihistaminic activity by in vitro and in vivo screening methods and data were verified analytically and statistically. The compound 4a, 4b, 5a and 5b showed significant H1-antihistaminiic activity than the reference standard chlorpheniramine maleate. The compound 6d, 6c, 5c and 4c exhibited significant antimicrobial activity.

scholarly journals Plant Products as Antimicrobial Agents

1999 ◽  
Vol 12 (4) ◽  
pp. 564-582 ◽  
Author(s):  
Marjorie Murphy Cowan
Keyword(s):  
Secondary Metabolites ◽  
Antimicrobial Agents ◽  
Antimicrobial Properties ◽  
Traditional Healers ◽  
In Vivo Studies ◽  
Current Status ◽  
The Public ◽  
The Earth

SUMMARY The use of and search for drugs and dietary supplements derived from plants have accelerated in recent years. Ethnopharmacologists, botanists, microbiologists, and natural-products chemists are combing the Earth for phytochemicals and “leads” which could be developed for treatment of infectious diseases. While 25 to 50% of current pharmaceuticals are derived from plants, none are used as antimicrobials. Traditional healers have long used plants to prevent or cure infectious conditions; Western medicine is trying to duplicate their successes. Plants are rich in a wide variety of secondary metabolites, such as tannins, terpenoids, alkaloids, and flavonoids, which have been found in vitro to have antimicrobial properties. This review attempts to summarize the current status of botanical screening efforts, as well as in vivo studies of their effectiveness and toxicity. The structure and antimicrobial properties of phytochemicals are also addressed. Since many of these compounds are currently available as unregulated botanical preparations and their use by the public is increasing rapidly, clinicians need to consider the consequences of patients self-medicating with these preparations.

scholarly journals DESIGN AND SYNTHESIS OF NOVEL 1-((DIMETHYLAMINO)METHYL)-3-(4-(3-(SUBSTITUTE DPHENYL)-4-OXOTHIAZOLIDIN-2-YL)PHENYLIMINO)-5-NITROINDOLIN-2-ONES AS POTENT ANTITUBERCULAR AGENTS

2019 ◽  
pp. 200-207
Author(s):  
KOSARAJU LAHARI ◽  
RAJA SUNDARARAJAN
Keyword(s):  
Antimicrobial Activity ◽  
Antimicrobial Agents ◽  
Biological Activities ◽  
Antimicrobial Activities ◽  
Mannich Bases ◽  
Proton Nuclear Magnetic Resonance ◽  
Design And Synthesis ◽  
Group Variation

Objective: Isatins have emerged as antimicrobial agents due to their broad spectrum of in vitro and in vivo antimicrobial activities. In addition, thiazolidinone also reported to possess various biological activities particularly antimicrobial activity. Due to the importance, we planned to synthesize compounds with isatin functionality coupled with thiazolidinone as possible antitubercular and antimicrobial agents which could furnish better therapeutic results. Methods: In vitro Mycobacterium tuberculosis method and agar streak dilution test are used to estimate antitubercular and antimicrobial potency of title analogs, respectively. Minimum inhibitory concentration of entire title compounds was determined against all tested microorganism such as M. tuberculosis, four Gram-positive, three Gram-negative bacteria, and two fungi. Results: A series of new thiazolidinone substituted Schiff and Mannich bases of 5-nitroisatins were designed and synthesized by a multistep synthesis from isatin. Structures of synthesized compounds are characterized using Fourier-transform infrared, proton nuclear magnetic resonance, mass spectroscopy, and bases of elemental analysis. Mild to good antitubercular and antimicrobial activity was showed by synthesized 5-nitroisatin analogs. The relationship between the biological activity and the functional group variation of the tested compounds was discussed. Conclusion: 3-(4-(3-(4-Aminophenyl)-4-oxothiazolidin-2-yl)phenylimino)-1-((dimethyl amino)methyl)-5-nitroindolin-2-one 6 and 3-(4-(3- (2-aminophenyl)-4-oxothiazolidin-2-yl)phenylimino)-1-((dimethylamino)methyl)-5-nitroindolin-2-one 13 were found to be the most potent compounds of this series which might be extended as a novel class of antimicrobial agents.

Deferiprone Stimulates Aged Dermal Fibroblasts via HIF-1α Modulation

2020 ◽  
Author(s):  
Andrea Pagani ◽  
B Manuela Kirsch ◽  
Ursula Hopfner ◽  
Matthias M Aitzetmueller ◽  
Elizabeth A Brett ◽  
...  
Keyword(s):  
Lactate Dehydrogenase ◽  
Cell Metabolism ◽  
Hypoxia Inducible Factor ◽  
Survival Rates ◽  
Iron Chelation ◽  
Iron Chelator ◽  
Dermal Fibroblasts ◽  
Topical Formulation

Abstract Background Hypoxia-inducible factor 1α (HIF-1α), a transcription factor responsible for tissue homeostasis and regeneration, presents reduced functionality in advanced age. In addition to absence of oxygen, sequestration of iron also stimulates HIF-1α. Therefore, we analyzed the efficacy of the iron-chelator deferiprone (DFP) at stimulating dermal fibroblasts. Objectives The main objective of this study was to quantify the DFP concentrations capable of stimulating dermal fibroblasts in vitro and to correlate the effective DFP concentrations with the ability of DFP to penetrate the epidermis, reach the dermis, and activate HIF-1α in vivo. Methods We measured cell proliferation, metabolic activity, HIF-1α expression, and lactate dehydrogenase levels of both young and aged fibroblasts after a 24-hour in vitro preconditioning with DFP. In addition, we evaluated cell survival rates and morphology with different cellular stainings. Finally, we performed a transdermal permeation study with a 1% DFP topical formulation to quantify the concentration required to reach the dermis. Results In vitro administration of iron-chelation therapy (156-312.5 µg/mL DFP ) on aged fibroblasts resulted in activation of various antiaging processes. The concentration required to reach the dermis within 24 hours was 1.5% (0.15 mg/mL), which corresponds well with the effective doses of our laboratory analyses. Conclusions The activation of HIF-1α by DFP enhances cell metabolism, proliferation, and survival of fibroblasts while reducing lactate dehydrogenase levels. Modulation of HIF-1α is linked to activation of key regeneration enzymes and proteins, and by proxy, antiaging. Therefore, the antiaging properties of DFP and its satisfactory dermal penetration make it a promising regenerative agent.

scholarly journals Chloramphenicol Resurrected: A Journey from Antibiotic Resistance in Eye Infections to Biofilm and Ocular Microbiota

2019 ◽  
Vol 7 (9) ◽  
pp. 278 ◽  
Author(s):  
Lorenzo
Keyword(s):  
Pathogenic Bacteria ◽  
Bacterial Resistance ◽  
Antimicrobial Agents ◽  
In Vivo Studies ◽  
Antibiofilm Activity ◽  
Eye Infections ◽  
Treatment And Prevention ◽  
Old Drugs

The advent of multidrug resistance among pathogenic bacteria is devastating the worth of antibiotics and changing the way of their administration, as well as the approach to use new or old drugs. The crisis of antimicrobial resistance is also due to the unavailability of newer drugs, attributable to exigent regulatory requirements and reduced financial inducements. The emerging resistance to antibiotics worldwide has led to renewed interest in old drugs that have fallen into disuse because of toxic side effects. Thus, comprehensive efforts are needed to minimize the pace of resistance by studying emergent microorganisms and optimize the use of old antimicrobial agents able to maintain their profile of susceptibility. Chloramphenicol is experiencing its renaissance because it is widely used in the treatment and prevention of superficial eye infections due to its broad spectrum of activity and other useful antimicrobial peculiarities, such as the antibiofilm properties. Concerns have been raised in the past for the risk of aplastic anemia when chloramphenicol is given intravenously. Chloramphenicol seems suitable to be used as topical eye formulation for the limited rate of resistance compared to fluoroquinolones, for its scarce induction of bacterial resistance and antibiofilm activity, and for the hypothetical low impact on ocular microbiota disturbance. Further in-vitro and in vivo studies on pharmacodynamics properties of ocular formulation of chloramphenicol, as well as its real impact against biofilm and the ocular microbiota, need to be better addressed in the near future.

A Practical Look at the Clinical Usefulness of the Beta-Lactam/Beta-Lactamase Inhibitor Combinations

1996 ◽  
Vol 30 (10) ◽  
pp. 1130-1140 ◽  
Author(s):  
Susan M. Hart ◽  
Elaine M. Bailey
Keyword(s):  
English Language ◽  
Antimicrobial Agents ◽  
In Vivo Studies ◽  
Patient Specific ◽  
Beta Lactamase ◽  
Beta Lactam ◽  
Intraabdominal Infections ◽  
Lactamase Inhibitor

OBJECTIVE: To aid clinicians in developing an approach to the use of intravenous beta-lactam/beta-lactamase inhibitors on a patient-specific basis. To achieve this, the pharmacology, in vitro activity, and clinical use of the intravenous beta-lactam/beta-lactamase inhibitor combinations in the treatment of selected infections seen in hospitalized patients are discussed. DATA IDENTIFICATION: An English-language literature search using MEDLINE (1987–1995); Index Medicus (1987–1995); program and abstracts of the 32nd (1992), 33rd (1993), 34th (1994), and 35th (1995) Interscience Conference on Antimicrobial Agents and Chemotherapy; bibliographic reviews of review articles; and package inserts. STUDY SELECTION: In vitro and in vivo studies on the pharmacokinetics, microbiology, pharmacology, and clinical effectiveness of ampicillin/sulbactam, ticarcillin/clavulanate, and piperacillin/tazobactam were evaluated. DATA SYNTHESIS: Many properties of the beta-lactam/beta-lactamase inhibitor combinations are similar. Differences in dosing, susceptibilities, and clinical applications are important considerations for clinicians. Potential roles for these agents in the clinical setting include pneumonia, intraabdominal infections, and soft tissue infections. A short discussion on susceptibility data interpretation is also presented. CONCLUSIONS: There are important differences among the available beta-lactam/beta-lactamase inhibitor combinations, such as spectra of activity, which need to be considered in choosing an agent for a patient-specific case. These products can be useful alternatives to conventional two- to three-drug regimens in mixed infections such as foot infections in patients with diabetes and hospital-acquired intraabdominal infections.

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