Toxicities of new substitutions of Dihydrochromeno (3, 4-b) chromenes compounds on the cancer cell line MOLT4 cell line

Background: Chemotherapy resistance of cancers have become a big challenge in modern medicine. Recently, in order to overcome the drug resistance issue, producing novel drug which used with previous ones as multidrug treatment became an alternative. One of the compounds that have drawn much attention in this regard is chromenes. Chromenes havea heterocyclic structure with gamma benzopyrone, and anti-canceractivities. Studies tried to produce new derivative of chromenes which have better effect on cancer therapy. In this investigation we produced four novel derivatives of chromenes and studied the effect of these compounds on the human acute lymphoblastic leukemia cell line ofMOLT4.Materials and methods A series of novel 4-hydroxycoumarinhas been synthesized via multi-step protocol.The structure of the new compound was established using spectroscopicmethod (H-NMR, C-NMR). MOLT4cells were cultured in RPMI 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 the MTT assay and cell counting afterdifferent incubation times (24, 48, 72 h).Result These compounds decreased viability of the MOLT4 cells in a time- and dose-dependent manner.Notably,meaningful differenceswere found between all concentrations and control groups. However, C2 had fewer IC50 in comparison to other ones. Interestingly, this derivatives showed significantly cell toxicity at the concentration of nano-Molar, while previously reported ones have cell toxicity at micro-Molar concentrations.Conclusion Dihydrochromeno (3, 4-b) chromenes have anti-neoplastic effects on MOLT4 by inducing of apoptosis. Further studies are needed to find exact mechanisms of its effect.

Keywords:

Chromene , Cytotoxicity , MOLT4 , apoptosis