Yıldız Mehmet Taha, Osmaniye Derya, Saglik Begum Nurpelin, Levent Serkan, Kurnaz Recep, Ozkay Yusuf, Kaplancıklı Zafer Asım
Hamidiye Faculty of Health Sciences, University of Health Sciences, Istanbul, Turkey.
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Anadolu University, Eskişehir, Turkey.
J Mol Recognit. 2024 Sep;37(5):e3089. doi: 10.1002/jmr.3089. Epub 2024 Jun 18.
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 IC = 0.123 + 0.005 μM. The interaction of the compound with the enzyme active site was clarified by molecular dynamics studies.
抗炎药物的频繁使用以及现有药物的副作用使得对新化合物的需求持续存在。为此，合成了本研究中常用的抗炎化合物氟比洛芬和布洛芬类化合物，并阐明了它们的结构。与布洛芬和氟比洛芬一样，这些化合物含有苯乙酸残基。另一方面，它含有仲胺残基。因此，计划即使稍微降低非甾体抗炎药最大的副作用——酸度。评估了这些化合物的估计药物代谢动力学参数。除了内服，抗炎化合物的局部应用也非常重要。因此，还计算了这些化合物的皮肤渗透率值。并且发现它与参考药物相容。通过体外实验测试了所得化合物的COX酶抑制作用。化合物2a对COX-1酶显示出显著活性，IC50 = 0.123 ± 0.005 μM。通过分子动力学研究阐明了该化合物与酶活性位点的相互作用。
