Pharmacological Exploitation of Non-Steroidal Anti-inflammatory Drugs as Potential Sources of Novel Antibacterial Agents

2019 ◽  
Vol 17 (2) ◽  
pp. 81-92
Author(s):  
Ebrahim M. Yimer ◽  
Ousman A. Mohammed ◽  
Seid I. Mohammedseid

The ever-increasing threat of bacterial infections and antimicrobial resistance calls for a global effort to deal with this problem. This fast and universal dissemination of antimicrobialresistant bacterial strains resulted in the diminution of therapeutic alternatives for various infectious diseases. Besides, the unaffordability of efficacious antimicrobials coupled with the occurrence of unpleasant adverse effects calls for the exploration of alternative agents with possible antibacterial effect. All these challenges of microbes have posed new drives to the scientific communities. Researchers are now assessing the possible alternative antimicrobial agents for fighting bacterial infections and antimicrobial resistance. Therefore, this review emphasizes on the role of nonsteroidal anti-inflammatory agents as potential sources of novel antibacterial agents on which preliminary studies and randomized controlled trials had been performed. The review also deals with the possible antibacterial mechanism of actions and the likely effects of non-steroidal antiinflammatory drugs when combined along with conventional antibacterial agents.

Author(s):  
Viola Zaki ◽  
Ahmed EL-gamal ◽  
Yasmin Reyad

he present research carried out to study the common bacterial infections in Oreochromis niloticus (Nile tilapia) in Manzala area at Dakahlia governorate and possible antimicrobial agents used for treatment. A total number of 400 fish were randomly collected from Manzala private farms at Dakahlia governorate and subjected to the clinical, bacteriological and histopathological examination. The highest prevalence of bacterial isolates during the whole period of examination of naturally infected O.niloticus was recorded for A.hydrophila (22.66%), followed by V.alginolyticus (19.01%), V.parahemolyticus (13.80%), Streptococcus spp. (12.24%), A.caviae (11.72%), V.cholera (10.16%), A.salmonicida (7.55%), while the lowest prevalence was recorded for Klebsiella oxytoca (2.86%). The seasonal highest total prevalence of bacterial isolates from examined naturally infected O. niloticus was recorded in spring (30.21%), followed by autumn (28.39%), then summer (22.40%) and the lowest prevalence was recorded in winter (19.01%). Histopathological findings of the tissue samples which collected from different organs of naturally infected O.niloticus revealed that spleen show marked hemosiderosis and sever hemorrhage, gills showsever congestion of lamellar capillaries with marked aneurysm, necrosis and hemorrhage of lamellar epithelium and liver show sever hydropic degeneration and necrosis of hepatocytes, Ciprofloxacin was the most effective antibiotic against all isolated bacterial strains


2021 ◽  
Vol 22 (5) ◽  
pp. 2497
Author(s):  
Filippo Prencipe ◽  
Anna Zanfardino ◽  
Michela Di Napoli ◽  
Filomena Rossi ◽  
Stefano D’Errico ◽  
...  

The evolution of antibacterial resistance has arisen as the main downside in fighting bacterial infections pushing researchers to develop novel, more potent and multimodal alternative drugs.Silver and its complexes have long been used as antimicrobial agents in medicine due to the lack of silver resistance and the effectiveness at low concentration as well as to their low toxicities compared to the most commonly used antibiotics. N-Heterocyclic Carbenes (NHCs) have been extensively employed to coordinate transition metals mainly for catalytic chemistry. However, more recently, NHC ligands have been applied as carrier molecules for metals in anticancer applications. In the present study we selected from literature two NHC-carbene based on acridinescaffoldand detailed nonclassicalpyrazole derived mono NHC-Ag neutral and bis NHC-Ag cationic complexes. Their inhibitor effect on bacterial strains Gram-negative and positivewas evaluated. Imidazolium NHC silver complex containing the acridine chromophore showed effectiveness at extremely low MIC values. Although pyrazole NHC silver complexes are less active than the acridine NHC-silver, they represent the first example of this class of compounds with antimicrobial properties. Moreover all complexesare not toxic and they show not significant activity againstmammalian cells (Hek lines) after 4 and 24 h. Based on our experimental evidence, we are confident that this promising class of complexes could represent a valuable starting point for developing candidates for the treatment of bacterial infections, delivering great effectiveness and avoiding the development of resistance mechanisms.


1997 ◽  
Vol 41 (11) ◽  
pp. 2389-2393 ◽  
Author(s):  
Y Kashida ◽  
M Kato

Fluoroquinolone antibacterial agents have been reported to induce tendon lesions in juvenile rats. In the present study, we characterized fluoroquinolone-induced Achilles tendon lesions by comparing the effects of 10 fluoroquinolones and examining the potential of one of these antimicrobial agents, pefloxacin, to induce tendon lesions when coadministered with one of nine anti-inflammatory compounds. Among the 10 fluoroquinolones tested, fleroxacin and pefloxacin were the most toxic, inducing lesions at a dose of 100 mg/kg of body weight or more, while lomefloxacin, levofloxacin, and ofloxacin or sparfloxacin and enoxacin induced lesions at 300 mg/kg or more and 900 mg/kg, respectively. In contrast, norfloxacin, ciprofloxacin, and tosufloxacin had no effect even at the high dose of 900 mg/kg. The severity of the Achilles tendon lesions appeared to correlate with the structure of the substituent at the seventh position. Furthermore, pefloxacin-induced tendon lesions were inhibited by coadministration with dexamethasone and N-nitro-L-arginine methyl ester. Phenidone (1-phenyl-3-pyrazolidinone) and 2-(12-hydroxydodeca-5,10-diynyl)3,5,6-trimethyl-1,4-benzoqui none (AA861) also decreased the incidence of tendon lesions. In contrast, catalase, dimethyl sulfoxide, indomethacin, pyrilamine, and cimetidine did not modify these tendon lesions. These results suggest that nitric oxide and 5-lipoxigenase products partly mediate fluoroquinolone-induced tendon lesions.


Antibiotics ◽  
2022 ◽  
Vol 11 (1) ◽  
pp. 104
Author(s):  
James V. Rogers ◽  
Veronica L. Hall ◽  
Charles C. McOsker

Antimicrobial resistance (AMR) is a concerning global threat that, if not addressed, could lead to increases in morbidity and mortality, coupled with societal and financial burdens. The emergence of AMR bacteria can be attributed, in part, to the decreased development of new antibiotics, increased misuse and overuse of existing antibiotics, and inadequate treatment options for biofilms formed during bacterial infections. Biofilms are complex microbiomes enshrouded in a self-produced extracellular polymeric substance (EPS) that is a primary defense mechanism of the resident microorganisms against antimicrobial agents and the host immune system. In addition to the physical protective EPS barrier, biofilm-resident bacteria exhibit tolerance mechanisms enabling persistence and the establishment of recurrent infections. As current antibiotics and therapeutics are becoming less effective in combating AMR, new innovative technologies are needed to address the growing AMR threat. This perspective article highlights such a product, CMTX-101, a humanized monoclonal antibody that targets a universal component of bacterial biofilms, leading to pathogen-agnostic rapid biofilm collapse and engaging three modes of action—the sensitization of bacteria to antibiotics, host immune enablement, and the suppression of site-specific tissue inflammation. CMTX-101 is a new tool used to enhance the effectiveness of existing, relatively inexpensive first-line antibiotics to fight infections while promoting antimicrobial stewardship.


2019 ◽  
Vol 31 (6) ◽  
pp. 1246-1250
Author(s):  
RAMALINGAM KUNDENAPALLY ◽  
RAMESH DOMALA ◽  
B. SREENIVASULU

In an attempt to discover the new antibacterial agents to fight the bacterial infections, a series of 1,8-naphthyridine based 2-iminothiazolidin-4-one derivatives was synthesized by a straight-forward regioselective synthesis. 2-Phenyl-1,8-naphthyridin-3-amine (2) was reacted with acetyl or aroyl isothiocyantes to give the corresponding N-[(2-phenyl-1,8-naphthyridin-3-yl)carbamothioyl)]acetamide or benzamides (3a-e). Finally, the target compounds [N-(4-oxo-3-(2-phenyl-1,8-naphthyridin-3-yl)thiazolidin-2-ylidene)]acetamide or benzamides (4a-e) were obtained by the reaction of thiourea (3a-e) with chloroacetyl chloride in presence of pyridine. All the synthesized products were formed in good yields and their structures were characterized by spectral (IR, EI-MS and NMR) and physical data. The biological activity of title compounds was evaluated against the bacterial strains and found to be more potent.


Author(s):  
Maysa Serpa ◽  
Juliana Amália Fonte Bôa do Nascimento ◽  
Mirian Fátima Alves ◽  
Maria Isabel Maldonado Coelho Guedes ◽  
Adrienny Trindade Reis ◽  
...  

Antimicrobial resistance is a current and important issue to public health, and it is usually associated with the indiscriminate use of antimicrobials in animal production. This study aimed to evaluate the antimicrobial susceptibility profile in bacterial isolates from pigs with clinical respiratory signs in Brazil. One hundred sixty bacterial strains isolated from pigs from 51 pig farms in Brazil were studied. In vitro disk-diffusion method was employed using 14 antimicrobial agents: amoxicillin, penicillin, ceftiofur, ciprofloxacin, enrofloxacin, chlortetracycline, doxycycline, oxytetracycline, tetracycline, erythromycin, tilmicosin, florfenicol, lincomycin, and sulfadiazine/trimethoprim. The majority of isolates were resistant to at least one antimicrobial agent (98.75%; 158/160), while 31.25% (50/160) of the strains were multidrug resistant. Streptococcus suis and Bordetella bronchiseptica were the pathogens that showed higher resistance levels. Haemophilus parasuis showed high resistance levels to sulfadiazine/trimethoprim (9/18=50%). We observed that isolates from the midwestern and southern regions exhibited four times greater chance of being multidrug resistant than the isolates from the southeastern region studied. Overall, the results of the present study showed a great level of resistance to lincomycin, erythromycin, sulfadiazine/trimethoprim, and tetracycline among bacterial respiratory pathogens isolated from pigs in Brazil. The high levels of antimicrobial resistance in swine respiratory bacterial pathogens highlight the need for the proper use of antimicrobials in Brazilian pig farms.


2010 ◽  
Vol 54 (6) ◽  
pp. 2525-2533 ◽  
Author(s):  
Robert Bucki ◽  
Katarzyna Leszczyńska ◽  
Fitzroy J. Byfield ◽  
David E. Fein ◽  
Esther Won ◽  
...  

ABSTRACT The rising number of antibiotic-resistant bacterial strains represents an emerging health problem that has motivated efforts to develop new antibacterial agents. Endogenous cationic antibacterial peptides (CAPs) that are produced in tissues exposed to the external environment are one model for the design of novel antibacterial compounds. Here, we report evidence that disubstituted dexamethasone-spermine (D2S), a cationic corticosteroid derivative initially identified as a by-product of synthesis of dexamethasone-spermine (DS) for the purpose of improving cellular gene delivery, functions as an antibacterial peptide-mimicking molecule. This moiety exhibits bacterial killing activity against clinical isolates of Staphylococcus aureus, Pseudomonas aeruginosa present in cystic fibrosis (CF) sputa, and Pseudomonas aeruginosa biofilm. Although compromised in the presence of plasma, D2S antibacterial activity resists the proteolytic activity of pepsin and is maintained in ascites, cerebrospinal fluid, saliva, and bronchoalveolar lavage (BAL) fluid. D2S also enhances S. aureus susceptibility to antibiotics, such as amoxicillin (AMC), tetracycline (T), and amikacin (AN). Inhibition of interleukin-6 (IL-6) and IL-8 release from lipopolysaccharide (LPS)- or lipoteichoic acid (LTA)-treated neutrophils in the presence of D2S suggests that this molecule might also prevent systemic inflammation caused by bacterial wall products. D2S-mediated translocation of green fluorescent protein (GFP)-labeled glucocorticoid receptor (GR) in bovine aorta endothelial cells (BAECs) suggests that some of its anti-inflammatory activities involve engagement of glucocorticoid receptors. The combined antibacterial and anti-inflammatory activities of D2S suggest its potential as an alternative to natural CAPs in the prevention and treatment of some bacterial infections.


2019 ◽  
Vol 25 (16) ◽  
pp. 1861-1865 ◽  
Author(s):  
Naira Sahakyan ◽  
Margarit Petrosyan ◽  
Armen Trchounian

Overcoming the antibiotic resistance is nowadays a challenge. There is still no clear strategy to combat this problem. Therefore, the urgent need to find new sources of antibacterial agents exists. According to some literature, substances of plant origin are able to overcome bacterial resistance against antibiotics. Alkanna species plants are among the valuable producers of these metabolites. But there is a problem of obtaining the standardized product. So, this review is focused on the discussion of the possibilities of biotechnological production of antimicrobial agents from Alkanna genus species against some microorganisms including antibiotic resistant bacterial strains.


2017 ◽  
Vol 61 (1) ◽  
pp. 61-70 ◽  
Author(s):  
Katharina Richter ◽  
Freija Van den Driessche ◽  
Tom Coenye

Many bacterial infections in humans and animals are caused by bacteria residing in biofilms, complex communities of attached organisms embedded in an extracellular matrix. One of the key properties of microorganisms residing in a biofilm is decreased susceptibility towards antimicrobial agents. This decreased susceptibility, together with conventional mechanisms leading to antimicrobial resistance, makes biofilm-related infections increasingly difficult to treat and alternative antibiofilm strategies are urgently required. In this review, we present three such strategies to combat biofilm-related infections with the important human pathogen Staphylococcus aureus: (i) targeting the bacterial communication system with quorum sensing (QS) inhibitors, (ii) a ‘Trojan Horse’ strategy to disturb iron metabolism by using gallium-based therapeutics and (iii) the use of ‘non-antibiotics’ with antibiofilm activity identified through screening of repurposing libraries.


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