Bioactivity Studies of β-Lactam Derived Polycyclic Fused Pyrroli-Dine/Pyrrolizidine Derivatives in Dentistry: In Vitro, In Vivo and In Silico Studies.

Autor: Meiyazhagan G; Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Raju R; Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India., Winfred SB; Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Mannivanan B; Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Bhoopalan H; Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Shankar V; Department of Bioinformatics, Alagappa University, Karaikudi, Tamilnadu, India., Sekar S; Center for Toxicology and Developmental Research, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Venkatachalam DP; Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Pitani R; Department of Community Medicine, Sri Ramachandra University, Porur, Chennai Tamilnadu, India., Nagendrababu V; Department of Conservative Dentistry and Endodontics, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Thaiman M; Central Research Facility, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Devivanayagam K; Department of Conservative Dentistry and Endodontics, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India., Jayaraman J; Department of Bioinformatics, Alagappa University, Karaikudi, Tamilnadu, India., Ragavachary R; Department of Organic Chemistry, University of Madras, Guindy Campus, Chennai, Tamilnadu, India., Venkatraman G; Department of Human Genetics, Sri Ramachandra University, Porur, Chennai, Tamilnadu, India.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2015 Jul 17; Vol. 10 (7), pp. e0131433. Date of Electronic Publication: 2015 Jul 17 (Print Publication: 2015).
DOI: 10.1371/journal.pone.0131433
Abstrakt: 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.
Databáze: MEDLINE
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