Discovery of 2′,6-Bis(4-hydroxybenzyl)-2-acetylcyclohexanone, a Novel FtsZ Inhibitor

Autor: Hsuan-Yu J. Lin, Rachana Rao Battaje, Jinlong Tan, Munikumar Doddareddy, Hemendra Pal Singh Dhaked, Shalini Srivastava, Bryson A. Hawkins, Laith Mohammad Hilal Al-Shdifat, David E. Hibbs, Dulal Panda, Paul W. Groundwater
Jazyk: angličtina
Rok vydání: 2022
Předmět:
Zdroj: Molecules, Vol 27, Iss 20, p 6993 (2022)
Druh dokumentu: article
ISSN: 1420-3049
DOI: 10.3390/molecules27206993
Popis: Multi-drug resistance is increasing in the pathogenic bacterium S. pneumoniae, which is mainly responsible for meningitis and community-acquired pneumonia (CAP), highlighting the need for new anti-pneumococcal agents. We have identified a potential anti-pneumococcal agent, enol 3, which acts by hindering the cell division process by perturbing Z-ring dynamics inside the cell. Enol 3 was also shown to inhibit FtsZ polymerization and induce its aggregation in vitro but does not affect the activity of tubulin and alkaline phosphatase. Docking studies show that 3 binds near the T7 loop, which is the catalytic site of FtsZ. Similar effects on Z-ring and FtsZ assembly were observed in B. subtilis, indicating that 3 could be a broad-spectrum anti-bacterial agent useful in targeting Gram-positive bacteria. In conclusion, compound 3 shows strong anti-pneumococcal activity, prompting further pre-clinical studies to explore its potential.
Databáze: Directory of Open Access Journals
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