scholarly journals Rickettsia prowazekii methionine aminopeptidase as a promising target for the development of antibacterial agents

2017 ◽  
Vol 25 (3) ◽  
pp. 813-824 ◽  
Author(s):  
Travis R. Helgren ◽  
Congling Chen ◽  
Phumvadee Wangtrakuldee ◽  
Thomas E. Edwards ◽  
Bart L. Staker ◽  
...  
2020 ◽  
Vol 16 (4) ◽  
pp. 389-401 ◽  
Author(s):  
Hanane Boucherit ◽  
Abdelouahab Chikhi ◽  
Abderrahmane Bensegueni ◽  
Amina Merzoug ◽  
Jean-Michel Bolla

Background: The great emergence of multi-resistant bacterial strains and the low renewal of antibiotics molecules are leading human and veterinary medicine to certain therapeutic impasses. Therefore, there is an urgent need to find new therapeutic alternatives including new molecules in the current treatments of infectious diseases. Methionine aminopeptidase (MetAP) is a promising target for developing new antibiotics because it is essential for bacterial survival. Objective: To screen for potential MetAP inhibitors by in silico virtual screening of the ZINC database and evaluate the best potential lead molecules by in vitro studies. Methods: We have considered 200,000 compounds from the ZINC database for virtual screening with FlexX software to identify potential inhibitors against bacterial MetAP. Nine chemical compounds of the top hits predicted were purchased and evaluated in vitro. The antimicrobial activity of each inhibitor of MetAP was tested by the disc-diffusion assay against one Gram-positive (Staphylococcus aureus) and two Gram-negative (Escherichia coli & Pseudomonas aeruginosa) bacteria. Among the studied compounds, compounds ZINC04785369 and ZINC03307916 showed promising antibacterial activity. To further characterize their efficacy, the minimum inhibitory concentration was determined for each compound by the microdilution method which showed significant results. Results: These results suggest compounds ZINC04785369 and ZINC03307916 as promising molecules for developing MetAP inhibitors. Conclusion: Furthermore, they could therefore serve as lead molecules for further chemical modifications to obtain clinically useful antibacterial agents.


2018 ◽  
Vol 28 (8) ◽  
pp. 1376-1380
Author(s):  
Travis R. Helgren ◽  
Elif S. Seven ◽  
Congling Chen ◽  
Thomas E. Edwards ◽  
Bart L. Staker ◽  
...  

2019 ◽  
Vol 26 (15) ◽  
pp. 2690-2714
Author(s):  
Raivis Žalubovskis ◽  
Jean-Yves Winum

The utilization of bacterial metalloenzymes, especially ones not having mammalian (human) counterparts, has drawn attention to develop novel antibacterial agents to overcome drug resistance and especially multidrug resistance. In this review, we focus on the recent achievements on the development of inhibitors of bacterial enzymes peptide deformylase (PDF), metallo-β-lactamase (MBL), methionine aminopeptidase (MetAP) and UDP-3-O-acyl- N-acetylglucosamine deacetylase (LpxC). The state of the art of the design and investigation of inhibitors of bacterial metalloenzymes is presented, and challenges are outlined and discussed.


2020 ◽  
Vol 477 (14) ◽  
pp. 2679-2696
Author(s):  
Riddhi Trivedi ◽  
Kalyani Barve

The intestinal microbial flora has risen to be one of the important etiological factors in the development of diseases like colorectal cancer, obesity, diabetes, inflammatory bowel disease, anxiety and Parkinson's. The emergence of the association between bacterial flora and lungs led to the discovery of the gut–lung axis. Dysbiosis of several species of colonic bacteria such as Firmicutes and Bacteroidetes and transfer of these bacteria from gut to lungs via lymphatic and systemic circulation are associated with several respiratory diseases such as lung cancer, asthma, tuberculosis, cystic fibrosis, etc. Current therapies for dysbiosis include use of probiotics, prebiotics and synbiotics to restore the balance between various species of beneficial bacteria. Various approaches like nanotechnology and microencapsulation have been explored to increase the permeability and viability of probiotics in the body. The need of the day is comprehensive study of mechanisms behind dysbiosis, translocation of microbiota from gut to lung through various channels and new technology for evaluating treatment to correct this dysbiosis which in turn can be used to manage various respiratory diseases. Microfluidics and organ on chip model are emerging technologies that can satisfy these needs. This review gives an overview of colonic commensals in lung pathology and novel systems that help in alleviating symptoms of lung diseases. We have also hypothesized new models to help in understanding bacterial pathways involved in the gut–lung axis as well as act as a futuristic approach in finding treatment of respiratory diseases caused by dysbiosis.


Planta Medica ◽  
2014 ◽  
Vol 80 (16) ◽  
Author(s):  
AC Valle ◽  
L Rabelo ◽  
AL Magalhães ◽  
M Neves ◽  
I Maciel ◽  
...  

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