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Wiley Interdisciplinary Reviews.... Jan 2022Escalating medical expenses due to infectious diseases are causing huge socioeconomic pressure on mankind globally. The emergence of antibiotic resistance has further... (Review)
Review
Escalating medical expenses due to infectious diseases are causing huge socioeconomic pressure on mankind globally. The emergence of antibiotic resistance has further aggravated this problem. Drug-resistant pathogens are also capable of forming thick biofilms on biotic and abiotic surfaces to thrive in a harsh environment. To address these clinical problems, various strategies including antibacterial agent delivering matrices and bactericidal coatings strategies have been developed. In this review, we have discussed various types of polymeric vehicles such as hydrogels, sponges/cryogels, microgels, nanogels, and meshes, which are commonly used to deliver antibiotics, metal nanoparticles, and biocides. Compositions of these polymeric matrices have been elaborately depicted by elucidating their chemical interactions and potential activity have been discussed. On the other hand, various implant/device-surface coating strategies which exploit the release-active mechanism of bacterial killing are discussed in elaboration. This article is categorized under: Therapeutic Approaches and Drug Discovery > Nanomedicine for Cardiovascular Disease Implantable Materials and Surgical Technologies > Nanomaterials and Implants Therapeutic Approaches and Drug Discovery > Nanomedicine for Infectious Disease.
Topics: Anti-Bacterial Agents; Anti-Infective Agents; Biofilms; Coated Materials, Biocompatible; Surface Properties
PubMed: 34374498
DOI: 10.1002/wnan.1745 -
Medicinal Chemistry (Shariqah (United... 2020Numerous synthetic bile acid derivatives have been recognized for their various biological activities. Among these, bile acid amides have emerged as an attractive...
BACKGROUND
Numerous synthetic bile acid derivatives have been recognized for their various biological activities. Among these, bile acid amides have emerged as an attractive antibacterial agent. We herein illustrate the synthesis and antibacterial evaluation of deoxycholic acidamino alcohols conjugates.
OBJECTIVE
Design and Synthesis of novel deoxycholic acid-amino alcohol conjugates to investigate their antibacterial activity against E. coli and S. aureus.
METHODS
Novel deoxycholic acid-amino alcohol conjugates were synthesized, from conjugation of deoxycholic acid-NHS ester with amino alcohols. Various amino alcohols moieties were appended to the C24 position of deoxycholic acid to yield deoxycholic acid-amino alcohol conjugates. All the synthesized compounds were characterized by 1H NMR, 13C NMR, IR and massspectroscopy. The entire synthesized deoxycholic acid-amino alcohol conjugates were evaluated for their antibacterial activity against E. coli and S. aureus using the broth dilution method.
RESULTS
The outcome illustrated that some of the novel deoxycholic acid-amino alcohol conjugates exhibited enhanced anti-bacterial activities. Amongst them, deoxycholic acid-amino alcohol conjugate containing (-R)-2-aminocyclohexanol (1) demonstrated promising efficacy against both strains S. aureus ATCC 25923 (MIC 15 μg/mL) and E. coli ATCC 25922 (MIC 45 μg/mL) and was identified as a lead molecule.
CONCLUSION
Numbers of novel deoxycholic acid-amino alcohol conjugates were synthesized and their antimicrobial activities provided useful information that the potency was strongly depending on the structures of deoxycholic acid-amino alcohol conjugates.
Topics: Amino Alcohols; Anti-Bacterial Agents; Deoxycholic Acid; Drug Design; Escherichia coli; Microbial Sensitivity Tests; Molecular Structure; Staphylococcus aureus; Structure-Activity Relationship
PubMed: 30727909
DOI: 10.2174/1573406415666190206231002 -
Microbiological Research Jul 2022Antimicrobial peptides (AMPs) are considered alternatives to classical antibiotics and may become an excellent candidate for tackling antimicrobial resistance in...
Antimicrobial peptides (AMPs) are considered alternatives to classical antibiotics and may become an excellent candidate for tackling antimicrobial resistance in aquaculture. Designing novel antimicrobial peptides for curbing antimicrobial resistance in aquaculture is paramount in one health approach. In this study, a short and compositionally simple peptide, KK16, was designed. KK16 is amphipathic with a net charge of + 6. Molecular docking results revealed that KK16 has a strong affinity towards two virulence proteins of Aeromonas sobria; aerolysin and outer membrane protein (omp). The peptide was synthesised using Fmoc-chemistry, and its antimicrobial efficacy was evaluated in vitro against A.sobria, A. salmonicida, Edwardsiella tarda, A. hydrophila, Vibrio parahaemolyticus, Pseudomonas aeruginosa, Escherichia coli, Staphylococcus epidermidis and methicillin-resistant S. aureus. The KK16 AMP showed potent activity against the tested bacterial pathogens as revealed by the MIC and MBC, ranging from 7.81 to 500 µM, and 15-900 µM, respectively. Moreover, the peptide was stable at higher temperatures and retained its activity in presence of serum and salt. The peptide displayed less haemolytic and cytotoxic activity even at higher concentrations. In peptide-DNA binding assay, KK16 showed its binding potential with bacterial genomic DNA and thus, may interfere with replication. Fluorescent microscopy revealed the uptake of propidium iodide by peptide treated bacterial cells, indicating its membrane disruption activity. In in vivo experiment, KK16 peptide completely inhibited the growth of Saprolegnia parasitica fungus at ≥ 30 µM peptide concentrations in embryonated fish eggs. The results indicate that KK16 peptide is stable, possess potent antibacterial and antifungal activity, less cytotoxic to host cells, and hence may prove to be a promising anti-infective agent for combating common bacterial and fungal infections.
Topics: Animals; Anti-Bacterial Agents; Anti-Infective Agents; Bacteria; Escherichia coli; Fishes; Methicillin-Resistant Staphylococcus aureus; Microbial Sensitivity Tests; Molecular Docking Simulation; Peptides
PubMed: 35500455
DOI: 10.1016/j.micres.2022.127039 -
Journal of the American Veterinary... Aug 2023This article, as part of the Currents in One Health series, reviews the current state of diagnostics for synovial sepsis. Synovial sepsis is a condition that affects...
This article, as part of the Currents in One Health series, reviews the current state of diagnostics for synovial sepsis. Synovial sepsis is a condition that affects veterinary and human medicine and requires coordinated efforts from both parties, as well as environmental considerations to accurately diagnose and preserve effective treatments. The article discusses best practices to identify the causative agent in septic synovitis, trends in bacterial identification and antimicrobial resistance patterns across common bacterial species, and a one-health perspective to optimize diagnostics across species. Antimicrobial resistance is a challenge facing both human and veterinary medicine and requires mindful and attentive prescribing to reduce the development of antimicrobial resistance and preserve antimicrobials for future application. The current standard of care for bacterial identification in veterinary practice is culture and antimicrobial susceptibility; however, positive culture rates from synovial sepsis cases often remain < 50%. Recent developments in advanced bacterial identification present opportunities for improved bacterial identification in synovial sepsis. Increased bacterial isolation will also help guide empirical antimicrobial therapy. Utilizing information and recommendations from both the human and veterinary literature will improve timely and accurate bacterial identification and therefore rapid and effective treatment of synovial sepsis across species and limit the development of antimicrobial resistance.
Topics: Humans; Animals; Anti-Bacterial Agents; One Health; Drug Resistance, Bacterial; Sepsis; Anti-Infective Agents
PubMed: 37380157
DOI: 10.2460/javma.23.05.0227 -
Current Pharmaceutical Design 2021Pulmonary infections are an increasing problem in individuals and current therapies are lacking. Liposomes are spherical lipidic vesicles composed of phospholipid and...
BACKGROUND
Pulmonary infections are an increasing problem in individuals and current therapies are lacking. Liposomes are spherical lipidic vesicles composed of phospholipid and cholesterol. Liposomes have numerous advantages, such as biodegradability, biocompatibility, non-immunogenicity, lack of toxicity, controlled release properties and high stability.
OBJECTIVE
This work was carried out to construct a novel liposomal moxifloxacin formulation and examine its antimicrobial effects against Pseudomonas aeruginosa and Staphylococcus aureus.
METHODS
The liposomal moxifloxacin formulation was prepared by the thin-film hydration method. The bilayer was composed of cholesterol and phospholipid at 30:70 molar ratio. To prepare cationic liposomes, 5% cationic agent (CTAB) was added. The liposomes were reduced in size with the bath sonication technique. The liposomal characterizations were tested regarding vesicle size, surface charge and drug encapsulation efficacy. Microdilution method was used to determine the Minimum Inhibitory Concentration (MIC) against Pseudomonas aeruginosa and Staphylococcus aureus of the free drug, neutral and cationic moxifloxacin liposomes.
RESULTS
The size of the liposomes was 50-70 nm. The zeta potential of neutral and cationic vesicles was ∼0 and +22 mV. The MIC values against Pseudomonas aeruginosa of the free drug, neutral and cationic moxifloxacin liposomes were 10, 5 and 2.5, respectively. The MICs against Staphylococcus aureus of the free drug, neutral and cationic moxifloxacin liposomes were 1, 1 and 0.5, respectively.
CONCLUSION
This study demonstrates that the encapsulation of moxifloxacin into liposomes (especially cationic vesicles) could enhance antimicrobial properties.
Topics: Anti-Bacterial Agents; Humans; Liposomes; Microbial Sensitivity Tests; Moxifloxacin; Nanoparticles; Pseudomonas aeruginosa
PubMed: 32611289
DOI: 10.2174/1381612826666200701152618 -
Molecules (Basel, Switzerland) Sep 2019Antibiotic resistance is a global health concern and a current threat to modern medicine and society. New strategies for antibiotic drug design and delivery offer a... (Review)
Review
Antibiotic resistance is a global health concern and a current threat to modern medicine and society. New strategies for antibiotic drug design and delivery offer a glimmer of hope in a currently limited pipeline of new antibiotics. One strategy involves conjugating iron-chelating microbial siderophores to an antibiotic or antimicrobial agent to enhance uptake and antibacterial potency. Cefiderocol (S-649266) is a promising cephalosporin-catechol conjugate currently in phase III clinical trials that utilizes iron-mediated active transport and demonstrates enhanced potency against multi-drug resistant (MDR) Gram-negative pathogens. Such molecules demonstrate that siderophore-antibiotic conjugates could be important future medicines to add to our antibiotic arsenal. This review is written in the context of the chemical design of siderophore-antibiotic conjugates focusing on the differing siderophore, linker, and antibiotic components that make up conjugates. We selected chemically distinct siderophore-antibiotic conjugates as exemplary conjugates, rather than multiple analogues, to highlight findings to date. The review should offer a general guide to the uninitiated in the molecular design of siderophore-antibiotic conjugates.
Topics: Anti-Bacterial Agents; Clinical Trials as Topic; Drug Design; Ferrous Compounds; Humans; Peptides; Siderophores
PubMed: 31514464
DOI: 10.3390/molecules24183314 -
Advanced Healthcare Materials Oct 2023In the surgical treatment of urinary diseases, ureteral stents are commonly used interventional medical devices. Although polymer ureteral stents with polyurethane as...
In the surgical treatment of urinary diseases, ureteral stents are commonly used interventional medical devices. Although polymer ureteral stents with polyurethane as the main constituent are widely used in the clinic, the need for secondary surgery to remove them and their propensity to cause bacterial infections greatly limit their effectiveness. To satisfy clinical requirements, an electrospinning-based strategy to fabricate PLGA ureteral stents with silver@graphdiyne is innovated. Silver (Ag) nanoparticles are uniformly loaded on the surface of graphdiyne (GDY) flakes. It is found that the incorporation of Ag nanoparticles into GDY markedly increases their antibacterial properties. Subsequently, the synthesized and purified Ag@GDY is homogeneously blended with poly(lactic-co-glycolic acid) (PLGA) as an antimicrobial agent, and electrospinning along with high-speed collectors is used to make tubular stents. The antibacterial effect of Ag@GDY and the porous microstructure of the stents can effectively prevent bacterial biofilm formation. Furthermore, the stents gradually decrease in toughness but increase in strength during the degradation process. The cellular and subcutaneous implantation experiments demonstrate the moderate biocompatibility of the stents. In summary, considering these performance characteristics and the technical feasibility of the approach taken, this study opens new possibilities for the design and application of biodegradable ureteral stents.
Topics: Silver; Metal Nanoparticles; Anti-Infective Agents; Stents; Anti-Bacterial Agents; Nanocomposites
PubMed: 37256720
DOI: 10.1002/adhm.202300885 -
Molecules (Basel, Switzerland) Aug 2023Rakicidin B1 was isolated and purified from the culture broth of a marine sp. as a potent anti-cancer agent, and lately the compound and its derivatives have firstly...
Rakicidin B1 was isolated and purified from the culture broth of a marine sp. as a potent anti-cancer agent, and lately the compound and its derivatives have firstly been found to possess anti- (CD) activity but with high cytotoxicity. Herein, following our previous discovery on anti-CD activity of Rakicidin B1, structure modification was performed at the OH position of Rakicidin B1 and a new Rakicidin B1-PEG hybrids FIMP2 was facilely designed and synthesized by conjugating the PEG2000 with the scaffolds of Rakicidin B1 via the linkage of carbamate. The cytotoxicity of the FIMP2 was first evaluated against three different cancer cell lines, including HCT-8 cells, PANC-1, and Caco-2, with IC values at 0.519 μM, 0.815 μM, and 0.586 μM, respectively. Obviously, as compared with a positive control group treated with Rakicidin B1, the IC value of FIMP2 increased by nearly 91-fold, 50-fold, and 67-fold, suggesting that the PEGylation strategy significantly reduced the cytotoxicity of FIMP2. Thus, this preliminary result may be beneficial to increase its safety index (SI) value due to the decreased cytotoxicity of FIMP2. In addition, this decreased cytotoxicity of FIMP2 was further confirmed based on a zebrafish screening model in vivo. Thereafter, the anti-CD activity of FIMP2 was evaluated in vivo, and its efficacy to treat CDI was found to be better than that of vancomycin. The mortality and recurrence rate of FIMP2 is not as low compared with that of vancomycin; these results demonstrated that compound FIMP2 is a new, promising anti-CD agent with significant efficacy against CD recurrence with low cytotoxicity towards bodies.
Topics: Humans; Animals; Anti-Bacterial Agents; Vancomycin; Caco-2 Cells; Zebrafish; Clostridioides difficile
PubMed: 37630404
DOI: 10.3390/molecules28166152 -
ChemMedChem Dec 2021Carbon monoxide (CO) has been known as an endogenous signaling molecule in addition to an air pollutant. It plays a critical role in many physiological and pathological... (Review)
Review
Carbon monoxide (CO) has been known as an endogenous signaling molecule in addition to an air pollutant. It plays a critical role in many physiological and pathological processes. Therefore, CO has been recognized as a potent therapeutic agent for the treatment of numerous diseases such as cancers, rheumatoid arthritis, and so on. Instead of direct CO inhalation, two main categories of CO-releasing molecules (CORMs) (i. e., metal carbonyls and nonmetallic CO donors) have been developed to safely and locally deliver CO to target tissues. In this minireview, we summarize the recent achievements of CORMs on antibacterial applications. It appears that the antibacterial activity of CORMs is different from CO gas, which is tightly correlated to not only the types of CORMs applied but also the tested bacterial strains. In some circumstances, the antibacterial mechanisms are debated and need to be clarified. We hope more attention can be paid to this emerging field and new antibacterial agents with a low risk of drug resistance can be developed.
Topics: Anti-Bacterial Agents; Bacteria; Carbon Monoxide; Microbial Sensitivity Tests; Molecular Structure; Organometallic Compounds
PubMed: 34613654
DOI: 10.1002/cmdc.202100555 -
Amphiphilic quaternized chitosan: Synthesis, characterization, and anti-cariogenic biofilm property.Carbohydrate Polymers Feb 2022Hydrophobized chitosan derivatives, hexyl chitosan (HCS), dodecyl chitosan (DCS), and phthaloyl chitosan (PhCS) of approximately 30 and 50% degree of substitution (%DS)...
Hydrophobized chitosan derivatives, hexyl chitosan (HCS), dodecyl chitosan (DCS), and phthaloyl chitosan (PhCS) of approximately 30 and 50% degree of substitution (%DS) reacted with glycidyltrimethylammonium chloride (GTMAC) to incorporate hydrophilic positively charged groups of N-[(2-hydroxyl-3-trimethylammonium)propyl] and yielded amphiphilic quaternized chitosan derivatives. They can assemble into spherical nanoparticles with a hydrodynamic diameter of ~100-300 nm and positive ζ-potential values (+15 to +56). Their anti-biofilm efficacy was evaluated against the dental caries pathogen, Streptococcus mutans. Among all derivatives, the one having 30%DS of hexyl group and prepared by reacting with 1 mol equivalent of GTMAC (HCS-GTMAC) showed the best performance in terms of its aqueous solubility, the lowest minimum inhibitory concentration (138 μg/mL) and the minimum bactericidal concentration (275 μg/mL) which are superior to the unmodified chitosan. Its equivalent anti-biofilm efficacy to that of chlorhexidine suggests that it can be a greener antibacterial agent for oral care formulations.
Topics: Anti-Bacterial Agents; Biofilms; Carbohydrate Conformation; Chitosan; Microbial Sensitivity Tests; Particle Size; Streptococcus mutans; Surface-Active Agents
PubMed: 34893285
DOI: 10.1016/j.carbpol.2021.118882