Halogenated 2-amino-4H-pyrano[3,2-h]quinoline-3-carbonitriles as antitumor agents and structure–activity relationships of the 4-, 6-, and 9-positions

A series of halogenated 2-amino-4-aryl-4H-pyrano[3,2-h]quinoline-3-carbonitrile derivatives were prepared via interaction of 8-hydroxyquinoline, 5-chloro-8-hydroxyquinoline, and 8-hydroxy-2-methylquinoline with various α-cyanocinnamonitriles. The assignments of the structure of all synthesized compounds were based on spectral data. The cytotoxic activities of the synthesized compounds against four human tumor cell lines MCF-7, HCT-116, HepG-2, and A549 in comparison with the reference drugs Vinblastine and Colchicine were determined by microculture tetrazolium assay. Several compounds showed significant cytotoxic activity. The structure–activity relationship studies reported that the substitution at 4-, 6-, and 9-positions in several 2-amino-4H-pyrano[3,2-h]quinoline nucleus with the specific halogen atom and lipophilicity increases the ability of the molecule against the different cell lines.