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

Abstract

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