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Unveiling Therapeutic Potential: Targeting IFusobacterium nucleatum/I’s Lipopolysaccharide Biosynthesis for Endodontic Infections—An In Silico Screening Study
Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Dr...
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Published in: | International journal of molecular sciences 2024-04, Vol.25 (8) |
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creator | Boreak, Nezar Alrajab, Ethar Awad Nahari, Rayan Ali Najmi, Loay Ebrahim Masmali, Muhannad Ali Ghawi, Atiah Abdulrahman Al Moaleem, Mohammed M Alhazmi, Majed Yahya Maqbul, Abdulrahman Abdullah |
description | Complex microbial communities have been reported to be involved in endodontic infections. The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies. |
doi_str_mv | 10.3390/ijms25084239 |
format | article |
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The microorganisms invade the dental pulp leading to pulpitis and initiating pulp inflammation. Fusobacterium nucleatum is a dominant bacterium implicated in both primary and secondary endodontic infections. Drugs targeting the molecular machinery of F. nucleatum will minimize pulp infection. LpxA and LpxD are early acyltransferases involved in the formation of lipid A, a major component of bacterial membranes. The identification of leads which exhibit preference towards successive enzymes in a single pathway can also prevent the development of bacterial resistance. A stringent screening strategy utilizing physicochemical and pharmacokinetic parameters along with a virtual screening approach identified two compounds, Lomefloxacin and Enoxacin, with good binding affinity towards the early acyltransferases LpxA and LpxD. Lomefloxacin and Enoxacin, members of the fluoroquinolone antibiotic class, exhibit wide-ranging activity against diverse bacterial strains. Nevertheless, their effectiveness in the context of endodontic treatment requires further investigation. This study explored the potential of Lomefloxacin and Enoxacin to manage endodontic infections via computational analysis. Moreover, the compounds identified herein serve as a foundation for devising novel combinatorial libraries with enhanced efficacy for endodontic therapeutic strategies.</abstract><pub>MDPI AG</pub><doi>10.3390/ijms25084239</doi></addata></record> |
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subjects | Analysis Biosynthesis Drug resistance Enoxacin Gram-negative bacteria Health aspects Infection Lipids Lomefloxacin Transferases |
title | Unveiling Therapeutic Potential: Targeting IFusobacterium nucleatum/I’s Lipopolysaccharide Biosynthesis for Endodontic Infections—An In Silico Screening Study |
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