Design, synthesis, and molecular docking study of novel quinoline-based bis-chalcones as potential antitumor agents

A novel series of quinoline-based symmetrical and unsymmetrical bis-chalcones was synthesized via a Claisen-Schmidt condensation reaction between 3-formyl-quinoline/quinolone derivatives with acetone or arylidene acetones, respectively, by using KOH/MeOH/H2O as a reaction medium. Twelve of the obtained compounds were evaluated for their in vitro cytotoxic activity against 60 different human cancer cell lines according to the National Cancer Institute protocol. Among the screened compounds, the symmetrical N-butyl bis-quinolinyl-chalcone 14g and the unsymmetrical quinolinyl-bis-chalcone 17o bearing a 7-chloro-substitution on the N-benzylquinoline moiety and 4-hydroxy-3-methoxy substituent on the phenyl ring, respectively, exhibited the highest overall cytotoxicity against the evaluated cell lines with a GI(50) range of 0.16-5.45 mu M, with HCT-116 (GI(50) = 0.16) and HT29 (GI(50) = 0.42 mu M) (colon cancer) representing best-case scenarios. Notably, several GI(50) values for these compounds were lower than those of the reference drugs doxorubicin and 5-FU. Docking studies performed on selected derivatives yielded very good binding energies in the active site of proteins that participate in key carcinogenic pathways.

Automated summary

A series of quinoline-based compounds were synthesized and evaluated for their cytotoxic activity against cancer cells, with two compounds showing promising anticancer effects with lower GI(50) values than reference drugs. Docking studies revealed strong binding energies in proteins involved in key carcinogenic pathways.