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Medicinal Chemistry

Author(s): Shaista Qayyum, Almas Jabeen*, Sajda Ashraf, Faiza Seraj, Khalid Mohammad Khan, Rafat Ali Siddiqui and Zaheer Ul-Haq*

DOI: 10.2174/0115734064290905231228110023

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

Page: [443 - 451] Pages: 9

  • * (Excluding Mailing and Handling)

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.

Graphical Abstract

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