A Facile Synthesis and Antitumor Activity of Novel 2-Aryl-2,3- dihydro-1H-pyrrolo[3,4-b]quinoxalin-1-ones

Abstract

In the present investigation, a simple and facile synthesis of a range of structurally novel and intriguing quinoxaline-based isoindolin-1-ones 7a-q has been described through the one-step reaction of ethyl 3-bromomethylquinoxaline-2-carboxylate with arylamines or aliphatic amines in refluxing ethanol medium. A preliminary screening for their in vitro anti-tumor activity against A549 and HT29 using the MTT assay revealed that halo-substituted (F, Cl, Br, I) compounds 7h-k showed promising inhibitory activity, among which fluro-substituted 7h possessed the best activity against the two cell lines with the IC₅₀ values of 1.50 and 3.77 μg/mL, respectively, being much better than the reference Cisplatin. The molecular docking simulation was performed to position compound 7h into the EGFR active site to determine the probable binding model.

Keywords:

• Quinoxaline
• isoindolin-1-one
• one-step reaction
• anti-tumor activity

Additional information

Funding

Doctoral Startup Foundation of Liaoning Province (No. 2019-BS-004); Scientific Research Foundation of the Education Department of Liaoning Province (No. LQ2019006).