Synthesis, molecular dynamics simulation, and evaluation of biological activity of novel flurbiprofen and ibuprofen-like compounds

IF 2.3 4区生物学 Q3 BIOCHEMISTRY & MOLECULAR BIOLOGY

Journal of Molecular Recognition Pub Date : 2024-06-18 DOI:10.1002/jmr.3089

Mehmet Taha Yıldız, Derya Osmaniye, Begum Nurpelin Saglik, Serkan Levent, Recep Kurnaz, Yusuf Ozkay, Zafer Asım Kaplancıklı

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引用次数: 0

Abstract

The frequent use of anti-inflammatory drugs and the side effects of existing drugs keep the need for new compounds constant. For this purpose, flurbiprofen and ibuprofen-like compounds, which are frequently used anti-inflammatory compounds in this study, were synthesized and their structures were elucidated. Like ibuprofen and flurbiprofen, the compounds contain a residue of phenylacetic acid. On the other hand, it contains a secondary amine residue. Thus, it is planned to reduce the acidity, which is the biggest side effect of NSAI drugs, even a little bit. The estimated ADME parameters of the compounds were evaluated. Apart from internal use, local use of anti-inflammatory compounds is also very important. For this reason, the skin permeability values of the compounds were also calculated. And it has been found to be compatible with reference drugs. The COX enzyme inhibitory effects of the obtained compounds were tested by in vitro experiments. Compound 2a showed significant activity against COX-1 enzyme with an IC₅₀ = 0.123 + 0.005 μM. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies.

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新型氟比洛芬和布洛芬类化合物的合成、分子动力学模拟及生物活性评价。

由于消炎药的频繁使用和现有药物的副作用，人们一直需要新的化合物。为此，本研究合成了常用的消炎化合物氟比洛芬和类布洛芬化合物，并阐明了它们的结构。与布洛芬和氟比洛芬一样，这些化合物也含有苯乙酸残留物。另一方面，它含有一个仲胺残基。因此，计划将非甾体抗炎药物的最大副作用--酸度降低哪怕一点点。对化合物的估计 ADME 参数进行了评估。除内服外，消炎化合物的局部使用也非常重要。因此，还计算了化合物的皮肤渗透值。结果发现，这些化合物的皮肤渗透性与参考药物相符。体外实验测试了所获化合物对 COX 酶的抑制作用。化合物 2a 对 COX-1 酶具有明显的活性，其 IC50 = 0.123 + 0.005 μM。分子动力学研究明确了化合物与酶活性位点的相互作用。

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

Journal of Molecular Recognition 生物-生化与分子生物学

CiteScore

4.60

自引率

3.70%

发文量

审稿时长

2.7 months

期刊介绍： Journal of Molecular Recognition (JMR) publishes original research papers and reviews describing substantial advances in our understanding of molecular recognition phenomena in life sciences, covering all aspects from biochemistry, molecular biology, medicine, and biophysics. The research may employ experimental, theoretical and/or computational approaches. The focus of the journal is on recognition phenomena involving biomolecules and their biological / biochemical partners rather than on the recognition of metal ions or inorganic compounds. Molecular recognition involves non-covalent specific interactions between two or more biological molecules, molecular aggregates, cellular modules or organelles, as exemplified by receptor-ligand, antigen-antibody, nucleic acid-protein, sugar-lectin, to mention just a few of the possible interactions. The journal invites manuscripts that aim to achieve a complete description of molecular recognition mechanisms between well-characterized biomolecules in terms of structure, dynamics and biological activity. Such studies may help the future development of new drugs and vaccines, although the experimental testing of new drugs and vaccines falls outside the scope of the journal. Manuscripts that describe the application of standard approaches and techniques to design or model new molecular entities or to describe interactions between biomolecules, but do not provide new insights into molecular recognition processes will not be considered. Similarly, manuscripts involving biomolecules uncharacterized at the sequence level (e.g. calf thymus DNA) will not be considered.