Synthesis of new benzo[f]chromene-based heterocycles targeting anti-proliferative activity

Abstract

Abstract: In this article β-enaminonitrile 1 undergoes intramolecular cyclocondensation reaction under acidic conditions to generate novel chromeno[2,3-b]azet-9-one derivative 2 in good yield. Ring expansion of the four membered ring of the azet-2(1H)-one derivative 2 to six and/or seven membered rings was achieved via reaction of compound 2 with different nitrogen nucleophiles. A new series of benzochromeneone, benzochromenopyrimidine, and benzo[f]coumarin derivatives were prepared via reaction of β-enaminonitrile 1 with different C-electrophiles. The structures of the products have been affirmed on the basis of analytical and spectral data. The anti-proliferative activity of the newly synthesized compounds against two human epithelial cell lines; liver (HepG2) and breast (MCF-7) in addition to normal fibroblasts (WI-38) was investigated. Derivatives 4 and 10 had significant and selective anti-proliferative activity against liver and breast cancer cell lines without harming normal fibroblasts. Graphic abstract: [Figure not available: see fulltext.].