title: Secalonic acid D as a novel DNA topoisomerase I inhibitor from marine lichen-derived fungus Gliocladium sp. T31.
abstract: BACKGROUND
  DNA topoisomerase I (topo I) is an essential enzyme which regulates the conformational changes in DNA topology by cleaving and rejoining DNA strands during normal cell growth. The inhibitors of topo I represent a major class of anticancer drugs. In our projects to isolate new anticancer agents from marine-derived fungi, secalonic acid D (SAD) with inhibitory activity on topo I was isolated from the fermentation broth of marine lichen-derived fungus Gliocladium sp. T31, which was collected from marine sediments in South Pole.
  
  
  OBJECTIVE
  The inhibitory activity of SAD on topo I was investigated for the first time.
  
  
  METHODS
  The inhibitory effect of SAD on topo I was determined via in vitro supercoil relaxation assays and electrophoretic mobility shift assay (EMSA) using plasmid substrate, pBR322.
  
  
  RESULTS
  SAD displays a considerable inhibition on topo I in a dose-dependent manner with the minimum inhibitory concentration (MIC) of 0.4 µM. Unlike the prototypic DNA topo I poison camptothecin (CPT), SAD inhibits the binding of topo I to DNA but does not induce the formation of topo I-DNA covalent complexes.
  
  
  CONCLUSIONS
  SAD is an excellent topo I inhibitor and thus a significantly potential anticancer candidate.
authors.affiliation: Beijing Key Laboratory of Plant Resource Research and Development, College of Chemical and Environmental Engineering, Beijing Technology and Business University, Beijing, China. renhong@th.btbu.edu.cn
authors.forename: Ren
authors.initials: R
authors.lastname: Hong
mesh_terms: D059001:Aquatic Organisms / Q000378:metabolism; D002166:Camptothecin / Q000494:pharmacology; D053938:DNA Fragmentation; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D004278:DNA, Superhelical / Q000032:analysis; D024202:Electrophoretic Mobility Shift Assay; D005658:Fungi / Q000378:metabolism; D005822:Genetic Vectors; D020462:Gliocladium / Q000378:metabolism*; D006801:Humans; D020014:K562 Cells; D008011:Lichens / Q000378:metabolism; D009792:Oceans and Seas; D010957:Plasmids / Q000235:genetics; D059004:Topoisomerase I Inhibitors / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D044004:Xanthones / Q000302:isolation & purification / Q000378:metabolism / Q000494:pharmacology*
chemical_list: D004278:DNA, Superhelical; D059004:Topoisomerase I Inhibitors; D044004:Xanthones; C009218:secalonic acid; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin