3-chloromethylene-6-fluorothiochroman-4-one,A novel DNA Topoisomerase poison

3-chloromethylene-6-fluorothiochroman-4-one (cmft) is a novel thiochromanones derivative that has better anti-tumor activity. in this paper,we will compare the antitumor activity of the cis-trans isomers,and explore their inhibiting effects on human topoisomerase i and topoisomerase ii in cell free reaction system. the mtt method was used to study inhibition rates; the ao/eb double staining and tunel assay was used to assess proportion of apoptotic cells. the inhibition of cmft to topo i and ii could be identified by adding cmft solutions to topo-dna reaction mixtures and observing the relative quantities of relaxed strands and supercoils in electrophoresis assay. results showed that cmft had dramatic anti-tumor activities at low concentrations and the activity of cmft trans-isomer is more significant. use of ao/eb double staining and tunel indicated that cmft induces apoptosis. dna relaxation assays and dna cleavage and relegation assays were performed and showed a higher potential to interact with topoisomerase i (topo i) and topoisomerase ii (topo ii) and it was verified that cmft is a topo poison which could be one of the mechanisms that induce cell apoptosis. our results provide preliminary data for further investigation for the mechanism of cmft of the apoptotic mechanism.