New 3-aminorhodanine derivatives: Synthesis, characterization, docking study and biological activates

Abstract

Background: Epidermal growth factor receptor (EGFR) is seen in almost all cases of non-small cell lung cancer (NSCLC). As a result, targeting EGFR has become an attractive subject of research in fields such as antitumor research and the most important strategy for cancer treatment, in particular, in the treatment of non-small-cell lung malignancies using EGFR-targeting therapies. Methods: For this purpose, novel N- and 5- disubstituted aminorhodanine derivatives were synthesized by Schiff base and using a Knoevenagel condensation approach over two steps of reactions. Then, rhodanine derivatives were analyzed their cytotoxic effect on A549 lung cancer and Hdfn normal cell and compared the analysis result with erlotinib (anticancer drug) as standard to determine their activities on cancer cell and toxicity or safety on normal cell. Results: Synthetic compounds (2a1-2, 2b1-2) showed different effects at 24, 48 and 72h. The higher anticancer effect was seen for 2a2 and 2a1with IC50 10 μg/mL and 32.59 μg/mL, respectively, at 24h and 72 h. Also, they show high anticancer potency at 72h with low effect and high safety on human normal cell. Conclusions: Developing a new series of rhodanine derivatives and evaluating their anticancer activity is the main goal of the study. In silico and in vitro antitumor investigations for newly synthesized compounds with different properties and functional group in chemical structure revealed different activities against lung cancer cell. Compounds 2a1-2 which contain pyridine ring in their chemical structure showed more potent effect than the derivative that bearing furyl ring (2b1-2).