Biooriented Synthesis of Ibuprofen-Clubbed Novel Bis-Schiff Base Derivatives as Potential Hits for Malignant Glioma: In Vitro Anticancer Activity and In Silico Approach

Abstract

This research work is based on the synthesis of bis -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), 1 H NMR, and 13 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 50 values ranging from 5.75 ± 0.43 to 150.45 ± 0.20 μM. Among them, compound 5e (IC 50 = 5.75 ± 0.43 μM) was found as the most potent antiprolifarative agent, while 5f, 5b, 5a, 5n, 5r, 5s, 5g, 5q, 5i , and 5j exhibited good activity with IC 50 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.

“Synergistic Innovation: Crafting Indazole Derivatives for Advanced Anticancer, Antioxidant, and Antimicrobial Efficacy through Integrative Design and Holistic Evaluation”

“…This, in turn, has the potential to curtail their survival and proliferation. [38][39][40] Moreover, indazole derivatives exhibit significant potential in impeding angiogenesis, the intricate process responsible for the formation of new blood vessels that nourish and oxygenate developing tumors. By disrupting this crucial mechanism, indazole compounds can thwart the tumor's capacity to establish a robust vascular network, ultimately hampering its progression and metastatic potential.…”