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

IF 1.9 4区医学 Q3 CHEMISTRY, MEDICINAL

Medicinal Chemistry Pub Date : 2024-01-01 DOI:10.2174/0115734064290905231228110023

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

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引用次数: 0

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.

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双氯芬酸的噁二唑衍生物作为 B 细胞非霍奇金淋巴瘤的抗增殖剂：体外和硅学研究。

背景：目的：本研究旨在通过体外和硅学方法研究双氯芬酸的新型抗炎噁二唑衍生物作为抗淋巴瘤药物的潜力：方法：化合物（II）对滤泡淋巴瘤细胞和伯基特淋巴瘤细胞都有抗淋巴瘤活性，而化合物（V）只对滤泡淋巴瘤细胞有抑制作用。双氯芬酸（I）和衍生物（III、IV 和 VI）没有抗增殖作用。双氯芬酸（II）能明显抑制滤泡淋巴瘤细胞和伯基特淋巴瘤细胞中 BCL-2、p-38 MAPK 和 TGF-β 的表达，对正常人成纤维细胞（BJ）无毒性：结果：针对 BCL-2 的硅学研究表明，化合物（II）中的未取代硫基参与了与结合位点残基的关键相互作用：结论：化合物（II）是治疗 B 细胞非霍奇金淋巴瘤的潜在候选药物，值得作为新型抗淋巴瘤药物进一步开发。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Medicinal Chemistry 医学-医药化学

CiteScore

4.30

自引率

4.30%

发文量

109

审稿时长

12 months

期刊介绍： Aims & Scope Medicinal Chemistry a peer-reviewed journal, aims to cover all the latest outstanding developments in medicinal chemistry and rational drug design. The journal publishes original research, mini-review articles and guest edited thematic issues covering recent research and developments in the field. Articles are published rapidly by taking full advantage of Internet technology for both the submission and peer review of manuscripts. Medicinal Chemistry is an essential journal for all involved in drug design and discovery.