New Urea Derivatives as Potential Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Patil, Mahadev; Noonikara‐Poyil, Anurag; Joshi, Shrinivas D.; Patil, Shivaputra A.; Patil, Siddappa A.; Bugarin, Alejandro

doi:10.3390/antibiotics8040178

Cited by 27 publications

(15 citation statements)

References 35 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This feature may be resolved through chemical expansion, using a targeted medicinal chemistry approach. In fact, urea derivatives are present in a number of pharmacological drugs, are available commercially, and have shown antimicrobial activity ( Patil et al, 2019a , b ).…”

Section: Discussionmentioning

confidence: 99%

Fluorometric Liposome Screen for Inhibitors of a Physiologically Important Bacterial Ion Channel

et al. 2021

View full text Add to dashboard Cite

The bacterial K+ homeostasis machinery is widely conserved across bacterial species, and different from that in animals. Dysfunction in components of the machinery has an impact on intracellular turgor, membrane potential, adaptation to changes in both extracellular pH and osmolarity, and in virulence. Using a fluorescence-based liposome flux assay, we have performed a high-throughput screen to identify novel inhibitors of the KtrAB ion channel complex from Bacillus subtilis, a component of the K+ homeostasis machinery that is also present in many bacterial pathogens. The screen identified 41 compounds that inhibited K+ flux and that clustered into eight chemical groups. Many of the identified inhibitors were found to target KtrAB with an in vitro potency in the low μM range. We investigated the mechanisms of inhibition and found that most molecules affected either the membrane component of the channel, KtrB alone or the full KtrAB complex without a preference for the functional conformation of the channel, thus broadening their inhibitory action. A urea derivative molecule that inhibited the membrane component of KtrAB affected cell viability in conditions in which KtrAB activity is essential. With this proof-of-concept study, we demonstrate that targeting components of the K+ homeostasis machinery has the potential as a new antibacterial strategy and that the fluorescence-based flux assay is a robust tool for screening chemical libraries.

show abstract

Section: Discussionmentioning

confidence: 99%

Fluorometric Liposome Screen for Inhibitors of a Physiologically Important Bacterial Ion Channel

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The 3D structures of the ligands were mapped and converted using ChemBioDraw Ultra and ChemBio3D Ultra (Cambridge soft Corp., Waltham, MA, USA). Auto dock was used in the molecular docking study to predict the possibility of protein ligands binding to the molecules [50,51]. The grid was then concentrated on the center (40Å, 40Å, 40Å, 0.375Å, central coordinates x = −8.866, y = 25.474, and z = 4.447).…”

Section: Methodsmentioning

confidence: 99%

Screening of the Hepatotoxic Components in Fructus Gardeniae and Their Effects on Rat Liver BRL-3A Cells

Lan

et al. 2019

Molecules

View full text Add to dashboard Cite

Fructus Gardeniae (FG) is a common Chinese medicine and food. However, the toxicity of FG has drawn increasing concern, especially its hepatotoxicity. The purpose of this study was to screen the hepatotoxic components of FG and evaluate their effects on rat liver BRL-3A cells. The chemical composition of FG was determined by HPLC-ESI-MS. CCK-8 assay was used to evaluate the cytotoxicity of ten chemical components from FG, and then the toxic components with significant inhibitory activity were selected for further study. The results showed that geniposide, genipin, genipin-1-gentiobioside, gardenoside, and shanzhiside all suppress cells viability. Apoptosis assays further indicated that geniposide and its metabolite genipin are the main hepatotoxic components of FG. Pretreatment of cells with geniposide or genipin increased the levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP). The activities of superoxide dismutase (SOD) and glutathione (GSH) were decreased, while the malondialdehyde (MDA) level was increased. The cell contents of tumor necrosis factor (TNF-α), interleukin-6 (IL-6), and nitric oxide (NO) were also increased. Molecular docking simulations were used to investigate the mechanism of FG-induced hepatotoxicity, revealing that geniposide and genipin bind strongly to the pro-inflammatory factor TNFR1 receptor of the NF-κB and MAPK signaling pathways. The obtained results strongly indicate that the hepatotoxicity of FG is caused by iridoids compounds. Genipin had the most significant hepatotoxic effect. These toxic substances destroy the cell antioxidant defense system, increasing inflammatory injury to the liver cells and leading to apoptosis and even necrosis. Thus, this study lays a foundation for toxicology research into FG and its rational application.

show abstract

“…Other chemical compounds, novel urea derivatives, were created using one-step amine reactions using thiocyanates in toluene [ 138 ]. The compounds were tested on Enterococcus faecium , S. aureus , K. pneumoniae , A. baumannii , P. aeruginosa , and Enterobacter species (ESKAPE bacteria) and two fungi ( C. albicans and C. neoformans ).…”

Section: Newly Prospective Pharmaceutical Candidates To Mitigate Antimicrobial Resistancementioning

confidence: 99%

“…The compounds were tested on Enterococcus faecium , S. aureus , K. pneumoniae , A. baumannii , P. aeruginosa , and Enterobacter species (ESKAPE bacteria) and two fungi ( C. albicans and C. neoformans ). Several compounds showed moderate to excellent activities against A. baumannii , K. pneumonia , S. aureus , and fungi C. neoformans , while moderate to poor activities were found in E. coli , P. aeruginosa , and C. albicans , indicating their prospective use as new antibiotic candidates, especially towards A. baumannii with the highest inhibition percentage of 94.5% [ 138 ]. The mechanisms of these compounds were yet to be determined.…”

Section: Newly Prospective Pharmaceutical Candidates To Mitigate Antimicrobial Resistancementioning

confidence: 99%

Pharmaceutical Approaches on Antimicrobial Resistance: Prospects and Challenges

et al. 2021

View full text Add to dashboard Cite

The rapid increase in pathogenic microorganisms with antimicrobial resistant profiles has become a significant public health problem globally. The management of this issue using conventional antimicrobial preparations frequently results in an increase in pathogen resistance and a shortage of effective antimicrobials for future use against the same pathogens. In this review, we discuss the emergence of AMR and argue for the importance of addressing this issue by discovering novel synthetic or naturally occurring antibacterial compounds and providing insights into the application of various drug delivery approaches, delivered through numerous routes, in comparison with conventional delivery systems. In addition, we discuss the effectiveness of these delivery systems in different types of infectious diseases associated with antimicrobial resistance. Finally, future considerations in the development of highly effective antimicrobial delivery systems to combat antimicrobial resistance are presented.

show abstract

New Urea Derivatives as Potential Antimicrobial Agents: Synthesis, Biological Evaluation, and Molecular Docking Studies

Cited by 27 publications

References 35 publications

Fluorometric Liposome Screen for Inhibitors of a Physiologically Important Bacterial Ion Channel

Fluorometric Liposome Screen for Inhibitors of a Physiologically Important Bacterial Ion Channel

Screening of the Hepatotoxic Components in Fructus Gardeniae and Their Effects on Rat Liver BRL-3A Cells

Pharmaceutical Approaches on Antimicrobial Resistance: Prospects and Challenges

Contact Info

Product

Resources

About