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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

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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 11a–e/thioureas 11f–k, 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.

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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.

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Authors and Affiliations

  1. Department of Chemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, 517 502, India

    Subba Rao Devineni, Madhava Golla & Naga Raju Chamarthi

  2. Department of Biochemistry, Sri Venkateswara University, Tirupati, Andhra Pradesh, 517 502, India

    Balaji Meriga

  3. Department of Zoology, Sri Venkateswara University, Tirupati, Andhra Pradesh, 517 502, India

    Madhu Sudhana Saddala & Usha Rani Asupathri

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  1. Subba Rao Devineni
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Correspondence to Naga Raju Chamarthi.

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Devineni, S.R., Golla, M., Chamarthi, N.R. et al. 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. Med Chem Res 25, 751–768 (2016). https://doi.org/10.1007/s00044-016-1518-x

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