Synthesis, Anti-Proliferative Activity, DFT and Docking Studies of Some Novel Chloroquinoline-Based Heterocycles

Cancer is one of the leading causes of death. Quinoline is well known as one of the most potent pharmaceutically active scaffolds with remarkable pharmacological properties. So, in this article, we focused our efforts on the utility of the key scaffold N′-(1-(4-((7-chloroquinolin-4-yl)amino)phenyl)ethylidene)-2-cyanoacetohydrazide (5) in the synthesis of their novel heterocyclic compounds with potential as anticancer agents. Based on these preliminary screening results against four different human cancer cell lines (HepG2, MCF-7, HCT-116, and PC-3). Gratifyingly, compounds 9 and 16 showed the highest anticancer activity. Adenosine A2B receptor (A2BAR) was found to be the probable cellular target for both promising candidate compounds 9 and 16. The docking study of tested compounds 9 and 16 revealed that they bind more strongly to the A2BAR as compared to that of its co-crystalized ligand, suggesting that the anticancer activities of the tested compounds may be related to their ability to block the A2BAR receptor signaling in cancer cells, leading to cell death. Computational studies and countersurfaces of the novel compounds helped us clarify and interpret the compounds that have high and low anticancer activity. Noteworthy, the results of these studies are approximately compatible with what was done in vitro.