Medicinal Chemistry Research

, Volume 25, Issue 4, pp 751–768 | Cite as

2-Amino-2,3-dihydro-1H-2λ5-[1,3,2]diazaphospholo[4,5-b]pyridin-2-one-based urea and thiourea derivatives: synthesis, molecular docking study and evaluation of anti-inflammatory and antimicrobial activities

  • Subba Rao Devineni
  • Madhava Golla
  • Naga Raju Chamarthi
  • Balaji Meriga
  • Madhu Sudhana Saddala
  • Usha Rani Asupathri
Original Research

Abstract

A series of new class of P-heterocycle encompassing urea and thiourea derivatives, N-(substitutedphenyl)-N′-(2-oxo-2,3-dihydro-1H-2λ5-[1,3,2]diazaphospholo[4,5-b]pyridin-2-yl)ureas 11ae/thioureas 11fk, was accomplished from the precursor intermediate, 2-amino-2,3-dihydro-1H-2λ5-[1,3,2]diazaphospholo[4,5-b]pyridin-2-one, 9. The compound 9 was obtained by   cyclization of pyridine-2,3-diamine, 6 with POCl3 followed by amidation with NaNH2. The products were tested for their in vitro and in vivo anti-inflammatory activity, and in vitro antimicrobial activity including minimum inhibitory concentration. Compounds 11a, 11d and 11j exhibited comparable anti-inflammatory activity to the standard drug, diclofenac, both in in vitro and in vivo assays, which might be due to the presence of lipophilic functional groups, F, NO2 and CF3. The compounds 11c and 11j exhibited potential growth of inhibition against selected bacterial and fungal strains at lower minimum inhibitory concentrations, while most of the thiourea-linked analogues exhibited good antimicrobial activity. A molecular modelling study was performed on cyclooxygenase isoenzyme (COX-2) to investigate the hypothetical binding mode of the most active anti-inflammatory agents, and binding conformers were proposed.

Keywords

P-heterocycles Urea and thiourea derivatives Anti-inflammatory activity Antimicrobial activity Docking study Cyclooxygenase isoenzyme (COX-2) 

Notes

Acknowledgments

The authors DSR, GM and SMR gratefully acknowledge the financial support from the University Grant Commission (UGC), Government of India, by awarding the Senior Research Fellowship. The authors also express thanks to Hyderabad Central University, Osmania University and K. Naresh, Department of Biochemistry, S. V. University, for providing instrumentation facilities to characterize the compounds and biological data, respectively.

Conflict of interest

The authors have declared no conflict of interest.

Supplementary material

44_2016_1518_MOESM1_ESM.docx (2 mb)
Supplementary material 1 (DOCX 2080 kb)

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Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • Subba Rao Devineni
    • 1
  • Madhava Golla
    • 1
  • Naga Raju Chamarthi
    • 1
  • Balaji Meriga
    • 2
  • Madhu Sudhana Saddala
    • 3
  • Usha Rani Asupathri
    • 3
  1. 1.Department of ChemistrySri Venkateswara UniversityTirupatiIndia
  2. 2.Department of BiochemistrySri Venkateswara UniversityTirupatiIndia
  3. 3.Department of ZoologySri Venkateswara UniversityTirupatiIndia

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