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.
Laboratory of Cell Pharmacology, College of Pharmaceutical Sciences, Hebei University, 180 East Wusi Road, Baoding, Hebei Province, China.
Yitian
Y
Wang
Laboratory of Cell Pharmacology, College of Pharmaceutical Sciences, Hebei University, 180 East Wusi Road, Baoding, Hebei Province, China.
Juntao
J
Chen
Laboratory of Cell Pharmacology, College of Pharmaceutical Sciences, Hebei University, 180 East Wusi Road, Baoding, Hebei Province, China.
Rui
R
Shen
Laboratory of Cell Pharmacology, College of Pharmaceutical Sciences, Hebei University, 180 East Wusi Road, Baoding, Hebei Province, China.
Chunliu
C
Yang
Laboratory of Cell Pharmacology, College of Pharmaceutical Sciences, Hebei University, 180 East Wusi Road, Baoding, Hebei Province, China.
Zhengyue
Z
Ma
Laboratory of Cell Pharmacology, College of Pharmaceutical Sciences, Hebei University, 180 East Wusi Road, Baoding, Hebei Province, China.
Yuxin
Y
Liu
D000951:Antigens, Neoplasm / Q000378:metabolism; D017209:Apoptosis / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002839:Chromans / Q000737:chemistry / Q000494:pharmacology*; D002867:Chromones / Q000737:chemistry / Q000494:pharmacology*; D004249:DNA Damage; D004264:DNA Topoisomerases, Type I / Q000378:metabolism*; D004250:DNA Topoisomerases, Type II / Q000378:metabolism; D004273:DNA, Neoplasm / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism; D004268:DNA-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005260:Female; D006367:HeLa Cells; D006801:Humans; D007536:Isomerism; D009690:Nucleic Acid Conformation; D059004:Topoisomerase I Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors / Q000737:chemistry / Q000494:pharmacology*; D002583:Uterine Cervical Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000235:genetics / Q000473:pathology
C000602464:3-(chloromethylene)-6-flourothiochroman-4-one; D000951:Antigens, Neoplasm; D002839:Chromans; D002867:Chromones; D004273:DNA, Neoplasm; D004268:DNA-Binding Proteins; D059004:Topoisomerase I Inhibitors; D059005:Topoisomerase II Inhibitors; D004264:DNA Topoisomerases, Type I; C528909:TOP1 protein, human; D004250:DNA Topoisomerases, Type II