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Novel 2-(substituted phenyl Imino)-5-benzylidene-4-thiazolidinones as possible non-ulcerogenic tri-action drug candidates: synthesis, characterization, biological evaluation And docking studies

  • Pooja Chawla
  • Sourav Kalra
  • Raj Kumar
  • Ranjit Singh
  • Shailendra K. SarafEmail author
Original Research

Abstract

The present research was aimed at the synthesis and screening of 35 novel 2-(substituted phenyl imino)-5-benzylidene-4-thiazolidinones having different substitutions at imino phenyl and arylidene groups. The title compounds were synthesized by Knoevenagel condensation at the 5th position of the 4-thiazolidinone ring, in the presence of sodium acetate. The structures were assigned on the basis of spectral data. The compounds were screened for in vivo anti-inflammatory, antinociceptive and in vitro free-radical scavenging activities. The compounds exhibited significant activities when compared with standard drugs. The distinctive property of the derivatives was that none of them had an acidic group, like conventional NSAIDs, but exhibited significant in vivo activity in acute inflammation models. Further, the active compounds of each series were docked against cyclooxygeanase (COX)-2 enzyme using Glide module of Maestro 11.1 program. It was evident from the docking results that 3-chlorophenylimino and 2-chloro moiety on 5-benzylidene nucleus of the 4-thiazolidinone derivative (30) could easily fit into the COX-2-binding pocket, considered as critical interaction for COX-2 inhibition. Interestingly, some of the compounds exhibited the potential of becoming dual action or even triple action drug candidates, which could target degenerative disorders associated with excessive free-radical generation.

Keywords

4-thiazolidinones Anti-inflammatory Antinociceptive Free-radical scavenging Docking Knoevenagel condensation 

Notes

Acknowledgements

The authors are thankful to Central Drug Research Institute (CDRI) India for spectral characterization.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.

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Copyright information

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

Authors and Affiliations

  1. 1.Department of Pharmaceutical ChemistryIndo-Soviet Friendship College of Pharmacy (ISFCP)MogaIndia
  2. 2.Laboratory for Drug Design and Synthesis, Centre for Pharmaceutical Sciences and Natural Products, School of Basic and Applied SciencesCentral University of PunjabBathindaIndia
  3. 3.Adarsh Vijendra Institute of Pharmaceutical SciencesShobhit University, GangohSaharanpurIndia
  4. 4.Babu Banarasi Das Northern India Institute of TechnologyLucknowIndia

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