Synthesis, Molecular Properties and Evaluation of the Antitumor Activity of 2-Amino-6-Methoxy-4H-Benzo[h]Chromenes, 6-Methoxy-2-Oxo-2HBenzo[ h]Chromene

Background: Chromene, benzochromene and their derivatives have been studied extensively due to their biological and pharmacological activities. Benzochromene nucleus has been emerged as a promising and attractive scaffold in the development of potent antitumor agents. Objectives: Design a series of new 2-amino-4H-benzo[h]chromene derivatives and evaluated their antiproliferative activity against three human tumor cell MCF-7, HepG-2, and HCT-116. Materials and Methods: The 2-amino-4H-benzo[h]chromene-3-carbonitrile derivatives 3a-i were synthesized by reaction of 4-methoxy-1-naphthol 1 with α-cyano-4-substitutedcinnamonitriles 2a-i in ethanolic piperidine under reflux for 1 hr. Reaction of 1 with ethyl α-cyano-4-substitutedcinnamates 4a-g afforded ethyl 4H-benzo[h]chromene-3-carboxylates derivatives 5a-d,f,g and 6-methoxy-2-oxo-4-(4- methylphenyl)-2H-benzo[h]chromene-3-carbonitrile 6. The assignment structures 3, 5 and 6 were established on the basis of spectral data. Results: In this study, the anti-proliferative activity of the synthesized compounds 3a-i, 5a-d,f,g and 6 was examined in three human cancer cell lines, MCF-7, HCT-116 and HepG-2, using MTT colorimetric assay. Vinblastine and Colchicine were included in the experiments as a reference cytotoxic compound for the three cell lines.