In vitro antitumor evaluation of 4H-chromene-3-carbonitrile derivatives as a new series of apoptotic inducers

Apoptosis is a naturally occurring process by which a cell is directed to programmed cell death. Chemotherapy drugs affect the cancer cells by the apoptotic induction. During the present study, a series of 4H-chromene-3-carbonitrile was synthesized by one-pot method as the inducers of apoptosis. Cytotoxic effects of six compounds of 4H-chromene-3-carbonitrile were evaluated against five tumor cell lines, with the help of colorimetric 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Compound 4 showed significant cytotoxic activity and was selected for conjugation with the synthesized gold nanoparticles by aspartic acid. Also, we evaluated apoptosis induction capacity of the selected compound with the help of fluorescent dyes and DNA fragmentation. The result showed that the conjugated and non-conjugated forms of compound 4 were effective in inducing apoptosis and conjugated one had more efficiency and reduced the effective dose. Also, molecular modeling experiments involving compound 4 and colchicine binding site of tubulin dimer showed several strong hydrogen bonds and hydrophobic interactions to many important amino acid residues and GTP.