Ayaz Muhammad, Alam Aftab, Assad Mohammad, Javed Aneela, Islam Mohammad Shahidul, Rafiq Huma, Ali Mumtaz, Ahmad Waqar, Khan Ajmal, Latif Abdul, Al-Harrasi Ahmed, Ahmad Manzoor
Department of Chemistry, University of Malakand, Dir Lower, Khyber Pakhtunkhwa 18800, Pakistan.
College of Chemistry and Materials Science, Hebei Normal University, Shijiazhuang 050024, China.
ACS Omega. 2023 Dec 13;8(51):49228-49243. doi: 10.1021/acsomega.3c07216. eCollection 2023 Dec 26.
This research work is based on the synthesis of -Schiff base derivatives of the commercially available ibuprofen drug in outstanding yields through multistep reactions. Structures of the synthesized compounds were confirmed by the help of modern spectroscopic techniques including high-resolution electrospray ionization mass spectrometry (HR-ESI-MS), H NMR, and C NMR. The synthesized compounds were evaluated for their anticancer activity using a normal human embryonic kidney HEK293 cell and U87-malignant glioma (ATCC-HTB-14) as a cancer cell line. All of the synthesized compounds among the series exhibited excellent to less antiproliferative activity having IC values ranging from 5.75 ± 0.43 to 150.45 ± 0.20 μM. Among them, compound (IC = 5.75 ± 0.43 μM) was found as the most potent antiprolifarative agent, while , and exhibited good activity with IC values from 24.17 ± 0.46 to 43.71 ± 0.07 μM. These findings suggest that these cells (HEK293) are less cytotoxic to the activities of compounds and increase the cancer cell death in brain, while the lower cytotoxicity of the potent compounds in noncancerous cells suggests that these derivatives will provide promising treatment for patients suffering from brain cancer. The results of the docking study exposed a promising affinity of the active compounds toward casein kinase-2 enzyme, which shows green signal for cancer treatment.
本研究工作基于通过多步反应以优异产率合成市售布洛芬药物的 - 席夫碱衍生物。借助现代光谱技术,包括高分辨率电喷雾电离质谱(HR - ESI - MS)、氢核磁共振(H NMR)和碳核磁共振(C NMR),确认了合成化合物的结构。使用正常人胚肾HEK293细胞和U87 - 恶性胶质瘤(ATCC - HTB - 14)作为癌细胞系,对合成化合物的抗癌活性进行了评估。该系列中的所有合成化合物均表现出优异至较低的抗增殖活性,其半数抑制浓度(IC)值范围为5.75 ± 0.43至150.45 ± 0.20 μM。其中,化合物 (IC = 5.75 ± 0.43 μM)被发现是最有效的抗增殖剂,而 、 和 表现出良好的活性,IC值为24.17 ± 0.46至43.71 ± 0.07 μM。这些发现表明,这些细胞(HEK293)对化合物的活性细胞毒性较小,并增加了脑癌细胞的死亡,而强效化合物在非癌细胞中的较低细胞毒性表明,这些衍生物将为患有脑癌的患者提供有前景的治疗方法。对接研究结果揭示了活性化合物对酪蛋白激酶 - 2酶具有有前景的亲和力,这为癌症治疗显示出绿色信号。