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Medicinal Chemistry Research

, Volume 27, Issue 5, pp 1460–1471 | Cite as

Inhibitory effects of α, β-unsaturated carbonyl-based compounds and their pyrazoline derivatives on the phagocytosis of human neutrophils

  • Laiba Arshad
  • Ibrahim Jantan
  • Syed Nasir Abbas Bukhari
  • Shajarahtunnur Jamil
Original Research

Abstract

A series of α, β-unsaturated carbonyl-based compounds (curcumin analogs and chalcone derivatives) and their pyrazoline derivatives were investigated for their in vitro inhibitory effects on the phagocytosis of human neutrophils. The effects of the compounds on the chemotactic migration, CD11a/18 expression, phagocytic activity, and reactive oxygen species (ROS) production by human whole blood cells (WBC) and isolated human polymorphonuclear neutrophils (PMNs) were assessed by using 24-well cell migration assay kit, flow cytometer, Phagotest assay kit, and luminol/lucigenin-based chemiluminescence assay, respectively. Compounds 4, 5, 6, 13, 23, 33, 39, and 41 showed strong inhibitory activity against PMNs chemotaxis with IC50 values, ranging from 0.22–1.68 µM which were much lower than those of ibuprofen and curcumin (IC50 values 11.02 and 5.0 µM, respectively). All compounds showed low or moderate inhibition of cell adhesion molecule expression except for compound 15, while compounds 4, 5, 8, and 21 at 100, 25, and 6.25 μg/mL showed strong inhibition of opsonized bacteria engulfment by neutrophils with the highest suppressive effects exhibited by compound 21 at 37.4%. Compounds 4, 11, 13, 14, 24, 25, 27, 33, and 34 significantly suppressed ROS generation by PMNs and WBC. Compounds with N-methyl 4-piperidone and 4-piperidone linkers (4, 13, 14, 23, 24) and 2-pyrazoline-1-carboxamide and 2-pyrazoline-1-carbothioamide derivatives showed strong inhibition on chemotactic and phagocytic activities, and ROS production. The results suggest that some of the α, β-unsaturated carbonyl-based compounds strongly modulated the innate immune responses of phagocytes at different steps, highlighting their potential as a source of new immunomodulatory agents.

Keywords

α, β-Unsaturated carbonyl-based compounds Immunosuppressive effect Chemotaxis Phagocytosis Reactive oxygen species 

Notes

Acknowledgements

The authors thanked Universiti Kebangsaan Malaysia for providing the grant under the Dana Impak Perdana and Md. Areeful Haque for his technical assistance.

Funding

This work was supported by Universiti Kebangsaan Malaysia under the Dana Impak Perdana (grant number DIP-2015-013).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

Supplementary material

44_2018_2163_MOESM1_ESM.docx (29 kb)
Supplementary Information

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Drug and Herbal Research Center, Faculty of PharmacyUniversiti Kebangsaan MalaysiaKuala LumpurMalaysia
  2. 2.Pharmaceutical Chemistry Department, College of PharmacyJouf UniversitySakakaSaudi Arabia
  3. 3.Faculty of ScienceUniversiti Teknologi MalaysiaJohor BahruMalaysia

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