The Antitumor Compounds Targeted On DNA Topoisomerases Screening

OBJECTIVE: To explore the antitumor activity of compounds targeted onDNA topoisomerases (TOPO) screening experiment condition in vitro, inorder to establish experiment foundation for targeted on DNAtopoisomerases scale screening; apply to screen compounds and gropecytotoxicity compounds of mechanism .METHODS: The cytotoxicity ofcompounds on several human tumor cell lines were determinded by MTT assayand the results were expressed as IC₅₀ values;Topoisomeraseâ…¡wasextracted from mice Ehrlich ascites carcinoma cells by procedure ofIsabella et al and topoisomeraseâ… isolated from calf thymus waspurchased, the effect of compounds on DNA TOPO activity was measured byagarose gel electrophoresisusing Plasmid pBR322DNA as thesubstrate. RESULTS: The results showed that the IC₅₀ values of thecompounds on several human tumor cell lines were 0.06-29.37μg/ml. G,J compounds influneced obviously the activity of DNA TOPOâ… , which theinhibitory effect of them on DNA TOPOâ… activity were 8,16μg/mlrespectively; The TOPOâ…¡mediated DNA relaxations were completelyinhibited by cyg-11,cyg-18,yxd-15 compuonds at the concentrations of16μg/ ml. G,J compounds inhibited TOPOâ…¡and cyg-11,cyg-18,yxd-15compuonds inhibited TOPOâ… were inferior. The effect of topoisomeraseson the other compounds were feeble or sine. CONCLUSION: The fourteencompounds exhibited significant antimoor activity in vitro. G,Jcompounds targeted specifically TOPOâ… and the inhibitory of TOPOâ…¡on cyg-11,cyg-18,yxd-15 compounds may be high selection.