Molecular docking and simulation studies of some pyrazolone-based bioactive ligands targeting the NF-\(\kappa\)B signaling pathways

IF 3.9 2区化学 Q2 CHEMISTRY, APPLIED

Molecular Diversity Pub Date : 2023-06-20 DOI:10.1007/s11030-023-10668-w

Surya Philip, D. R. Sherin, T. K. Manoj Kumar, T. C. Badisha Banu, Reny Mary Roy

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引用次数: 0

Abstract

NF-κB has become a predominant regulator responsible for multiple physiological and pathological processes. NF-κB signaling pathway has canonical and non-canonical components which strategize the cancer-related metabolic processes. Non-canonical NF-κB pathways are known to contribute towards the chemoresistance of cancer cells. Consequently, NF-κB can be utilized as a potential therapeutic target for modifying the behaviour of tumor cells. In view of this, we herein report a series of pyrazolone-based bioactive ligands that potentially target NF- κB and, thereby, unveil their anticancer properties. The pharmacological screening of the synthesized compounds were carried out using various virtual screening techniques. The anticancer studies of synthesized pyrazolones showed that APAU exhibited the most potent effect against the MCF-7 cells with an IC₅₀ value of 30 μg/ml. Molecular docking studies revealed that the pyrazolones inhibited cell proliferation by targeting the NFκB signaling pathway. The molecular dynamics simulation studies predicted the stability and flexibility of pyrazolone-based bioactive ligands.

Graphical abstract

Abstract Image

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针对 NF-κ B 信号通路的一些吡唑酮类生物活性配体的分子对接和模拟研究。

NF-κB 已成为负责多种生理和病理过程的主要调节因子。NF-κB 信号通路有规范和非规范两种成分，它们对与癌症有关的代谢过程起着战略作用。众所周知，非规范的 NF-κB 通路有助于增强癌细胞的化疗抵抗力。因此，NF-κB 可被用作改变肿瘤细胞行为的潜在治疗靶点。有鉴于此，我们在此报告了一系列基于吡唑酮的生物活性配体，这些配体可能以 NF-κB 为靶点，从而揭示其抗癌特性。我们利用各种虚拟筛选技术对合成的化合物进行了药理筛选。对合成的吡唑酮类化合物的抗癌研究表明，APAU 对 MCF-7 细胞的作用最强，IC50 值为 30 μg/ml。分子对接研究表明，吡唑酮类化合物通过靶向 NFκB 信号通路抑制细胞增殖。分子动力学模拟研究预测了吡唑酮类生物活性配体的稳定性和灵活性。

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来源期刊

Molecular Diversity 化学-化学综合

CiteScore

7.30

自引率

7.90%

发文量

219

审稿时长

2.7 months

期刊介绍： Molecular Diversity is a new publication forum for the rapid publication of refereed papers dedicated to describing the development, application and theory of molecular diversity and combinatorial chemistry in basic and applied research and drug discovery. The journal publishes both short and full papers, perspectives, news and reviews dealing with all aspects of the generation of molecular diversity, application of diversity for screening against alternative targets of all types (biological, biophysical, technological), analysis of results obtained and their application in various scientific disciplines/approaches including: combinatorial chemistry and parallel synthesis; small molecule libraries; microwave synthesis; flow synthesis; fluorous synthesis; diversity oriented synthesis (DOS); nanoreactors; click chemistry; multiplex technologies; fragment- and ligand-based design; structure/function/SAR; computational chemistry and molecular design; chemoinformatics; screening techniques and screening interfaces; analytical and purification methods; robotics, automation and miniaturization; targeted libraries; display libraries; peptides and peptoids; proteins; oligonucleotides; carbohydrates; natural diversity; new methods of library formulation and deconvolution; directed evolution, origin of life and recombination; search techniques, landscapes, random chemistry and more;