Oxadiazole Derivatives of Diclofenac as an Anti-proliferative Agent for B-cell Non-Hodgkin Lymphoma: An In vitro and In Silico Studies

Med Chem. 2024;20(4):443-451. doi: 10.2174/0115734064290905231228110023.

Abstract

Background: Non-Hodgkin lymphoma of B cell origin is the common type of lymphoma- related malignancy with poor response rate with conventional front-line therapies.

Aim: The aim of the present study was to investigate the potential of new anti-inflammatory oxadiazole derivatives of Diclofenac as an anti-lymphoma agent through in vitro and in silico approaches.

Methods: Anti-lymphoma potential was evaluated by alamar blue technique. MTT assay employed for cytotoxicity. Gene and protein expression studies was performed by qRT-PCR and ELISA respectively. Docking studies was performed by using MOE program.

Results: Among five diclofenac derivatives, (II) showed promising anti-lymphoma effects, where it inhibited the expression of BCL-2, p-38 MAPK and TGF-β in both follicular and Burkitt's lymphoma cells and was non-toxic against normal human fibroblast cells. The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in (II) is involved in the crucial interactions with the binding site residue.

Conclusion: The compound (II) can be a potential therapeutic candidate for B-cell non-Hodgkin lymphoma and deserves further development as a novel anti-lymphoma agent.

Keywords: B-cells; Diclofenac; Non-Hodgkin lymphoma; alamar blue technique.; anti-inflammatory; anti-lymphoma.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation* / drug effects
  • Computer Simulation
  • Diclofenac* / chemistry
  • Diclofenac* / pharmacology
  • Drug Screening Assays, Antitumor
  • Humans
  • Lymphoma, B-Cell / drug therapy
  • Lymphoma, B-Cell / pathology
  • Molecular Docking Simulation*
  • Molecular Structure
  • Oxadiazoles* / chemical synthesis
  • Oxadiazoles* / chemistry
  • Oxadiazoles* / pharmacology
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Structure-Activity Relationship
  • Transforming Growth Factor beta / antagonists & inhibitors
  • Transforming Growth Factor beta / metabolism
  • p38 Mitogen-Activated Protein Kinases / metabolism

Substances

  • Oxadiazoles
  • Diclofenac
  • Antineoplastic Agents
  • Proto-Oncogene Proteins c-bcl-2
  • Transforming Growth Factor beta
  • p38 Mitogen-Activated Protein Kinases