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Medicinal Chemistry Research

, Volume 28, Issue 12, pp 2200–2217 | Cite as

Microwave-assisted synthesis of 11-substituted-3,3-dimethyl-2,3,4,5,10,11-hexahydrodibenzo[b,e][1,4]diazepin-1-one derivatives catalysed by silica supported fluoroboric acid as potent antioxidant and anxiolytic agents

  • Kavita Bhagat
  • Atamjit Singh
  • Suruchi Dhiman
  • Jatinder Vir Singh
  • Ramandeep Kaur
  • Gurinder Kaur
  • Harmandeep Kaur Gulati
  • Palwinder Singh
  • Raman Kumar
  • Rajan Salwan
  • Kajal Bhagat
  • Harbinder SinghEmail author
  • Sahil SharmaEmail author
  • Preet Mohinder Singh BediEmail author
Original Research
  • 59 Downloads

Abstract

Keeping in view the successive attributes of benzodiazepines on the central nervous system, we have synthesized a novel series of benzodiazepine derivatives as antioxidant and anxiolytic agents. All the compounds were obtained in good yield by facile synthesis. To check their antioxidant potential, DPPH (2,2-diphenyl-1-picrylhydrazyl) free radical scavenging assay was performed. Among all the synthetics seven derivatives (SD-3, SD-5, SD-7, SD-14, SD-18, SD-19, and SD-20) exhibited IC50 values ranging from 76 to 489 nM. These seven compounds were further evaluated to check their binding abilities towards the benzodiazepine binding site on GABAA receptors. Three best-fit ligands (SD-3, SD-14 and SD-20) were further evaluated for their anxiolytic effect by using three in vivo mice models i.e. Elevated Plus Maze, Light & Dark box, and Mirror Chamber model. The study revealed that compounds SD-3 and SD-20 showed the best anxiolytic effect as compared to standard drug diazepam even at an oral dose of 1.0 mg/kg.

Keywords

Benzodiazepines Antioxidant activity Molecular modelling studies In silico studies In vivo anxiolytic effect 

Notes

Acknowledgements

The authors are grateful to University Grants Commission (RGNF), Council of Scientific & Industrial Research (CSIR), Department of Science & Technology (WOS-A) and DST-FIST for providing funds and are also thankful to Guru Nanak Dev University, Amritsar for providing various facilities to carry out the research work.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2019_2447_MOESM1_ESM.docx (1.9 mb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Department of Pharmaceutical SciencesGuru Nanak Dev UniversityAmritsarIndia
  2. 2.University Institute of Pharmaceutical SciencesPanjab UniversityChandigarhIndia
  3. 3.Department of ChemistryGuru Nanak Dev UniversityAmritsarIndia

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