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FPX-113 attenuates inflammatory responses by deteriorating cytokines, neutrophil activity and mast cell degranulation via Akt/ NF- κB pathway

  • Prasanna RajagopalanEmail author
  • Ayed A Dera
  • Mohamad Ragab Abdalsamad
  • Majed Al Fayi
  • Abdulrahim Hakami
  • Harish C. Chandramoorthy
Original Article


Search of novel chemical compounds to manage disorders of inflammation is always on demand. Herein we report FPX-113 a novel small molecule to exhibit excellent anti-inflammatory properties in human whole blood (HWB), peripheral blood mononuclear cells (PBMCs), RBL-2H3 and THP-1 cells. FPX-113 showed an inhibition of TNF-α, IFN-γ, IL-2, IL-6, IL-8 and IL-17 release from HWB and PBMC with IC50 values of 364.6 nM, 505.2 nM, 160.2 nM, 369.1 nM 371.2 nM, 459 nM and 64.14 nM, 92.30 nM, 49.88 nM, 151.7 nM, 108.9 nM, 92.70 nM respectively. The compound inhibited neutrophil migration and elastase in a dose dependent way. Further, FPX-113 inhibited the degranulation of rat mast cell basophils in RBL-2H3 cells with an IC50 of 280.5 nM. A dose dependent inhibition of Akt phosphorylation in RBL-2H3 and THP-1 cells and down regulation of NF- κB in PBMCs, RBL-2H3 and THP-1 cells by FPX-113 were evidenced when induced with 5 μg/mL PHA + 50 ng/mL PMA for 30 min. Taken together, the results suggest FPX-113 exhibits anti-inflammatory mechanism signaled via Akt/ NF- κB pathway. These findings will provide a wide scope for FPX-113 and its close analogues to be developed as novel anti-inflammatory agents for various diseases.


Arylidene Inflammation Neutrophil Mast cells p-Akt 



Acid citrate dextrose


American Type Culture Collection


Dimethyl sulphoxide


2,4-Dinitrophenol- Bovine serum albumin


Enzyme linked immune sorbent assay


Fetal bovine serum


N-Formyl methionyl-leucyl-phenylalanine


Hanke’s Buffered Salt Solution


Human whole blood


Interferon gamma


Immunoglobin E




Potassium chloride


3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide


Novel chemical entity


Peripheral blood mono nucleocytes






Rat basophilic leukemia


Sodium dodecyl sulphate


Tris buffer saline


Tissue necrosis factor alpha


Micro molar



The authors extend their appreciation to the Deanship of Scientific Research at King Khalid University, Abha, Saudi Arabia, for funding this work through General Research Project under grant number (G.R.P.1/80/40).

Compliance with ethical standards

Conflict of interest

The authors hereby state that there is no any conflict of interest related to this study.


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Copyright information

© Institute of Molecular Biology, Slovak Academy of Sciences 2019

Authors and Affiliations

  1. 1.Department of Clinical Laboratory Sciences, College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia
  2. 2.Central Research Laboratory, College of Applied Medical SciencesKing Khalid UniversityAbhaSaudi Arabia
  3. 3.Research Center of Advanced MaterialsKing Khalid UniversityAbhaSaudi Arabia
  4. 4.Department of Microbiology & Clinical Parasitology and Center for Stem Cell Research, College of MedicineKing Khalid UniversityAbhaSaudi Arabia

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