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Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies.
- Source :
-
PloS one [PLoS One] 2015 Jul 17; Vol. 10 (7), pp. e0131433. Date of Electronic Publication: 2015 Jul 17 (Print Publication: 2015). - Publication Year :
- 2015
-
Abstract
- 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.
- Subjects :
- Animals
Anti-Bacterial Agents chemistry
Bicuspid microbiology
Biofilms
Computer Simulation
Drosophila melanogaster
Drug Evaluation, Preclinical
Enterococcus faecalis drug effects
Female
Humans
Mice, Inbred BALB C
Microbial Sensitivity Tests
Models, Molecular
Penicillin-Binding Proteins chemistry
Protein Binding
Pyrrolidines chemistry
Reactive Oxygen Species metabolism
Root Canal Irrigants chemistry
Root Canal Therapy
Salmonella typhimurium drug effects
beta-Lactams chemistry
Anti-Bacterial Agents pharmacology
Pyrrolidines pharmacology
Root Canal Irrigants pharmacology
beta-Lactams pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1932-6203
- Volume :
- 10
- Issue :
- 7
- Database :
- MEDLINE
- Journal :
- PloS one
- Publication Type :
- Academic Journal
- Accession number :
- 26185985
- Full Text :
- https://doi.org/10.1371/journal.pone.0131433