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Synthesis and molecular docking of pyrimidine incorporated novel analogue of 1,5-benzodiazepine as antibacterial agent

  • Apoorva Misra
  • Swapnil Sharma
  • Divya Sharma
  • Sunil Dubey
  • Achal Mishra
  • Dharma Kishore
  • Jaya Dwivedi
Regular Article

Abstract

A one-pot protocol involving nitrile-derived amidoxime of 1,5-benzodiazepine to synthesize its novel pyrimidine derivatives using DMAD and DABCO catalyst under microwave conditions has been described. The antibacterial activity of the synthesized compounds was examined against Gram-positive S. aureus and Gram-negative E. coli using broth micro-dilution assay. Low IC\(_{50}\) values for the synthesized compounds indicated their potential as antibacterial agents. Further, field emission scanning electron microscopic study and cell membrane leakage study ascertained that the test compounds have ability to cause cell lysis via bacterial cell membrane rupture and disintegration. In addition, molecular docking studies suggested that test compounds may act through bacterial DHFR inhibition.

Graphical Abstract

SYNOPSIS Novel pyrimidine-incorporated 1,5-benzodiazepine analogues through its nitrile-derived amidoxime using one-pot domino approach have been synthesized. Structures of all the compounds were established through IR, \(^{1}\hbox {H}\) NMR, \(^{13}\hbox {C}\) NMR and mass spectral data. Further, antibacterial activity test was performed using broth micro-dilution assay and the probable mode of action of compound (6) was examined via field emission scanning electron microscopy (FE-SEM) and molecular docking studies.

Keywords

1, 5-benzodiazepine pyrimidine domino synthesis antibacterial activity 

Notes

Acknowledgements

The authors are deeply grateful for the financial support provided by Department of Science and Technology (DST), New Delhi under the CURIE (Consolidation of University Research for Innovation and Excellence in Women Universities) Scheme and MHRD, New Delhi, Under Training and Research in Frontier Areas of Science and Technology (FAST) Scheme. Authors are also thankful to Dr. Saral Kumar Gupta, Head, Department of Physics, Banasthali Vidyapith, Banasthali, Rajasthan, India for extending FE-SEM facility.

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

12039_2018_1430_MOESM1_ESM.pdf (2.2 mb)
Supplementary material 1 (pdf 2296 KB)

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Copyright information

© Indian Academy of Sciences 2018

Authors and Affiliations

  1. 1.Department of ChemistryBanasthali VidyapithBanasthaliIndia
  2. 2.Department of PharmacyBanasthali VidyapithBanasthaliIndia
  3. 3.Department of PharmacyBirla Institute of Technology and Science, PilaniPilaniIndia

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