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

Shaista Qayyum; Almas Jabeen; Sajda Ashraf; Faiza Seraj; Khalid Mohammad Khan; Rafat Ali Siddiqui; Zaheer Ul-Haq

doi:10.2174/0115734064290905231228110023

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 Jan 25. doi: 10.2174/0115734064290905231228110023. Online ahead of print.

Authors

Shaista Qayyum¹, Almas Jabeen¹, Sajda Ashraf¹, Faiza Seraj², Khalid Mohammad Khan², Rafat Ali Siddiqui³, Zaheer Ul-Haq¹

Affiliations

¹ Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan.
² HEJ Research Institute of Chemistry, International Center for Chemical and Biological Sciences, University of Karachi, Karachi-75270, Pakistan.
³ Food Chemistry and Nutritional Science Research Laboratory, Virginia State University, Petersburg, USA.

PMID: 38279758
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.

Method: The compound (II) showed anti-lymphoma activity against both follicular and Burkitt's lymphoma cells, whereas compound (V) inhibited follicular lymphoma cells only. The diclofenac (I) and derivatives (III, IV and VI) exhibited no anti-proliferative effects. The (II) significantly 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 (BJ).

Result: The in silico studies against BCL-2 revealed that the unsubstituted Sulphur group in compound (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; Non-Hodgkin lymphoma; anti-inflammatory; anti-lymphoma; diclofenac.