Toxicities of New 10,11-Dihydrochromeno[4,3-b]chromene-6,8(7H,9H)-dione Derivatives on the Cancer Cell Line MOLT4

Background and Aims: Benzopyrones are a group of compounds including coumarins and chromenes. Chromenes have a heterocyclic structure with gamma benzopyran which has anticancer activities. In this investigation we studied the effect of 4 new derivatives of chromene compounds on the human acute lymphoblastic leukemia cell line MOLT4. Materials and Methods: The structure of the new compound was established using spectroscopic method (1H NMR, 13C NMR). MOLT4 cells were cultured in Roswell Park Memorial Institute 1640 medium with 10% fetal bovine serum. The cytotoxic effect of different concentrations (0, 50, 250, 500 and 1000 nM) of novel synthetic compounds were evaluated by MTT assay and cell counting after different incubation times (24, 48, 72 h). Expression levels of 3 genes related to apoptosis (p53, Bax, Fas) were measured using real-time quantitative polymerase chain reaction. Results: These compounds all decreased viability of the MOLT4 cells in a time- and dose-dependent manner. Also meaningful difference was found between all concentrations and control groups (p<0.05). The compound C2 had lower IC50 in comparison to other ones. Interestingly, these derivatives showed significantly cell toxicity at nano-molar concentrations, while previously-reported ones had activity at micro-molar concentrations. All three apoptotic genes revealed increased expression. Conclusions: 10,11-dihydrochromeno [4,3-b]chromene-6, 8(7H,9H)-dione derivatives have anti-neoplastic effects on MOLT4 leukemic cell line by induction of apoptosis. These comounds could then be a potential candidate for further investigations.