Reductive domino reaction to access chromeno[2,3-c]isoquinoline-5-amines with antiproliferative activities against human tumor cells

Abstract

An interaction of homophthalonitrile with salicylaldehydes proceeds as a novel domino reaction and results in the formation of nineteen 12H-chromeno[2,3-c]isoquinoline-5-amine derivatives. Four new bonds and two cycles are forged in a single synthetic operation, employing cheap and eco-friendly ammonium formate, acting both as a catalyst and a reducing agent. The in vitro cytotoxicity tests revealed antiproliferative activities against five human tumor cell lines, including the cisplatin-resistant ovarian carcinoma one (A2780cp8), with inhibitory potency data (IC₅₀) in the low micromolar range in most cases. Molecular docking calculations and fluorescence quenching studies revealed possible binding properties with DNA of the active compounds.

Keywords: Antiproliferative activity; DNA binding; Domino reaction.