Synthetic lanostane-type triterpenoids as inhibitors of DNA topoisomerase II.
DNA topoisomerase (Topo) II is one of the target enzymes for chemotherapeutic drug development. Lanostane-type triterpenoids with various functional groups (-Cl, -Br, -OMe, -CHO, -CN, -COOH, and -COOMe) at C-2 were synthesized from 3-oxolanost-9(11)-en-24S,25-diol (9) isolated from Pinus luchuensis and their inhibitory effects on Topo II activity and cytotoxic activities against A549 cells were examined. All the derivatives showed Topo II inhibitory effects with IC50 values ranging from 1.86 to 149.97 microM and cytotoxic activities with ED50 values ranging from 3.96 to 38.15 microM.
Wada
Shun-Ichi
S
Laboratory of Medicinal Chemistry, Osaka University of Pharmaceutical Sciences, 4-20-1 Nasahara, Takatsuki, Osaka 569-1094, Japan. wada@gly.oups.ac.jp
Tanaka
Reiko
R
D000970:Antineoplastic Agents / Q000494:pharmacology; D004354:Drug Screening Assays, Antitumor; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D007810:Lanosterol / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D008175:Lung Neoplasms / Q000188:drug therapy; D015394:Molecular Structure; D028223:Pinus / Q000737:chemistry*; D024301:Plant Bark / Q000737:chemistry*; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004791:Enzyme Inhibitors; D059005:Topoisomerase II Inhibitors; D014315:Triterpenes; D007810:Lanosterol