Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies
| العنوان: | Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies |
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| المؤلفون: | Venkateshbabu Nagendrababu, Rajesh Raju, Kandaswamy Devivanayagam, Gowri Meiyazhagan, Venkatesh Shankar, Bhavani Mannivanan, Ganesh Venkatraman, Hemadev Bhoopalan, Sathiya Sekar, Deepa Parvathi Venkatachalam, Raghunathan Ragavachary, Sofi Beaula Winfred, Malini Thaiman, Ravishankar Pitani, Jeyakanthan Jayaraman |
| المصدر: | PLoS ONE, Vol 10, Iss 7, p e0131433 (2015) PLoS ONE |
| بيانات النشر: | Public Library of Science (PLoS), 2015. |
| سنة النشر: | 2015 |
| مصطلحات موضوعية: | Models, Molecular, Salmonella typhimurium, Penicillin binding proteins, Pyrrolidines, Science, Drug Evaluation, Preclinical, Dentistry, Microbial Sensitivity Tests, beta-Lactams, Enterococcus faecalis, Flow cytometry, chemistry.chemical_compound, In vivo, medicine, Animals, Humans, Penicillin-Binding Proteins, Bicuspid, Computer Simulation, Mice, Inbred BALB C, Multidisciplinary, biology, medicine.diagnostic_test, Root Canal Irrigants, business.industry, biology.organism_classification, Anti-Bacterial Agents, Root Canal Therapy, Drosophila melanogaster, Mechanism of action, chemistry, Biofilms, Pyrrolizidine, Medicine, Female, medicine.symptom, Antibacterial activity, business, Reactive Oxygen Species, Ex vivo, Research Article, Protein Binding |
| الوصف: | The antibacterial activity of β-lactam derived polycyclic fused pyrrolidine/pyrrolizidine derivatives synthesized by 1, 3-dipolar cycloaddition reaction was evaluated against microbes involved in dental infection. Fifteen compounds were screened; among them compound 3 showed efficient antibacterial activity in an ex vivo dentinal tubule model and in vivo mice infectious model. In silico docking studies showed greater affinity to penicillin binding protein. Cell damage was observed under Scanning Electron Microscopy (SEM) which was further proved by Confocal Laser Scanning Microscope (CLSM) and quantified using Flow Cytometry by PI up-take. Compound 3 treated E. faecalis showed ROS generation and loss of membrane integrity was quantified by flow cytometry. Compound 3 was also found to be active against resistant E. faecalis strains isolated from failed root canal treatment cases. Further, compound 3 was found to be hemocompatible, not cytotoxic to normal mammalian NIH 3T3 cells and non mutagenic. It was concluded that β-lactam compound 3 exhibited promising antibacterial activity against E. faecalis involved in root canal infections and the mechanism of action was deciphered. The results of this research can be further implicated in the development of potent antibacterial medicaments with applications in dentistry. |
| اللغة: | English |
| تدمد: | 1932-6203 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::70139aa91da7363cb76cae3793c3bab9Test https://doaj.org/article/255c4a7d665d4571a544843372958a88Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....70139aa91da7363cb76cae3793c3bab9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 19326203 |
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