Hawash Mohammed, Jaradat Nidal, Hameedi Saba, Mousa Ahmed
Department of Pharmacy, Faculty of Medicine and Health Sciences, An-Najah National University, P.O. Box 7, Nablus, 00970 Palestine.
Department of Biomedical Sciences, Faculty of Medicine and Health Sciences, An-Najah National University, Nablus, 00970 Palestine.
BMC Chem. 2020 Sep 7;14(1):54. doi: 10.1186/s13065-020-00706-1. eCollection 2020 Dec.
Non-steroidal anti-inflammatory drugs are among the most used drugs. They are competitive inhibitors of cyclooxygenase (COX). Twelve novel compounds (aryl acetate and aryl acetic acid groups) were synthesized in this work in order to identify which one was the most potent and which group was most selective towards COX1 and COX2 by using an in vitro COX inhibition assay kit. The cytotoxicity was evaluated for these compounds utilizing MTS assay against cervical carcinoma cells line (HeLa). The synthesized compounds were identified using FTIR, HRMS, H-NMR, and C-NMR techniques. The results showed that the most potent compound against the COX1 enzyme was 4f with IC = 0.725 µM. The compound 3b showed potent activity against both COX1 and COX2 with IC = 1.12 and 1.3 µM, respectively, and its selectivity ratio (0.862) was found to be better than Ketoprofen (0.196). In contrast, compound 4d was the most selective with a COX1/COX2 ratio value of 1.809 in comparison with the Ketoprofen ratio. All compounds showed cytotoxic activity against the HeLa Cervical cancer cell line at a higher concentration ranges (0.219-1.94 mM), and the most cytotoxic compound was 3e with a CC value of 219 µM. This was tenfold more than its IC values of 2.36 and 2.73 µM against COX1 and COX2, respectively. In general, the synthesized library has moderate activity against both enzymes (i.e., COX1 and COX2) and ortho halogenated compounds were more potent than the meta ones.
非甾体抗炎药是使用最为广泛的药物之一。它们是环氧化酶（COX）的竞争性抑制剂。在本研究中合成了12种新型化合物（芳基乙酸酯和芳基乙酸基团），以便通过体外COX抑制检测试剂盒确定哪一种化合物效力最强，以及哪一类基团对COX1和COX2具有最高的选择性。利用MTS检测法评估了这些化合物对子宫颈癌细胞系（HeLa）的细胞毒性。使用傅里叶变换红外光谱（FTIR）、高分辨质谱（HRMS）、氢核磁共振（H-NMR）和碳核磁共振（C-NMR）技术对合成的化合物进行了鉴定。结果表明，对COX1酶效力最强的化合物是4f，其半数抑制浓度（IC）=0.725 μM。化合物3b对COX1和COX2均显示出强效活性，其IC值分别为1.12 μM和1.3 μM，并且发现其选择性比（0.862）优于酮洛芬（0.196）。相比之下，与酮洛芬的比例相比，化合物4d的选择性最高，COX1/COX2比值为1.809。所有化合物在较高浓度范围（0.219 - 1.94 mM）下均对HeLa子宫颈癌细胞系显示出细胞毒性活性，细胞毒性最强的化合物是3e，其半数细胞毒性浓度（CC）值为219 μM。这比其对COX1和COX2的IC值（分别为2.36 μM和2.73 μM）高出十倍。总体而言，合成文库对两种酶（即COX1和COX2）均具有中等活性，邻位卤代化合物比间位卤代化合物的效力更强。
