| Autor: |
Lin HJ; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia., Battaje RR; Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India., Tan J; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia., Doddareddy M; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia., Dhaked HPS; Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India., Srivastava S; Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India., Hawkins BA; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia., Al-Shdifat LMH; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia., Hibbs DE; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia., Panda D; Department of Biosciences and Bioengineering, Indian Institute of Technology Bombay, Mumbai 400076, India.; National Institute of Pharmaceutical Education and Research, Nagar 160062, India., Groundwater PW; Sydney Pharmacy School, Faculty of Medicine and Health, The University of Sydney, Sydney, NSW 2006, Australia. |
| Abstrakt: |
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. |
