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

ABONIA, RODRIGO; NOGUERAS, MANUEL; LAALI, KENNETH K.; INSUASTY, DANIEL; INSUASTY, BRAULIO; COBO, JUSTO; GARCÍA, STEPHANIE; QUIROGA, JAIRO; BOROSKY, GABRIELA L.

ARCHIV DER PHARMAZIE.

WILEY-V C H VERLAG GMBH

Lugar: Weinheim; Año: 2021

0365-6233

A novel series of quinoline‐based symmetrical and unsymmetrical bis‐chalcones wassynthesized via a Claisen?Schmidt condensation reaction between 3‐formylquinoline/quinolone derivatives with acetone or arylidene acetones, respectively, byusing KOH/MeOH/H2O as a reaction medium. Twelve of the obtained compoundswere evaluated for their in vitro cytotoxic activity against 60 different humancancer cell lines according to the National Cancer Institute protocol. Among thescreened compounds, the symmetrical N‐butyl bis‐quinolinyl‐chalcone 14g andthe unsymmetrical quinolinyl‐bis‐chalcone 17o bearing a 7‐chloro‐substitution onthe N‐benzylquinoline moiety and 4‐hydroxy‐3‐methoxy substituent on the phenylring, respectively, exhibited the highest overall cytotoxicity against the evaluatedcell lines with a GI50 range of 0.16?5.45 μM, with HCT‐116 (GI50 = 0.16) and HT29(GI50 = 0.42 μM) (colon cancer) representing best‐case scenarios. Notably, severalGI50 values for these compounds were lower than those of the reference drugsdoxorubicin and 5‐FU. Docking studies performed on selected derivatives yieldedvery good binding energies in the active site of proteins that participate in keycarcinogenic pathways.