<> "The repository administrator has not yet configured an RDF license."^^ . <> . . . "Tubulin-perturbing naphthoquinone spiroketals"^^ . "Several natural and synthetic naphthoquinone spiroketals are potent inhibitors of the thioredoxin-thioredoxin reductase redox system. Based on the antimitotic and weak antitubulin actions noted for SR-7 ([8-(furan-3-ylmethoxy)- 1-oxo-1,4-dihydronaphthalene-4-spiro-2′-naphtho[1″,8″-de] [1′,3′][dioxin]), a library of related compounds was screened for tubulin-perturbing properties. Two compounds, TH-169 (5′-hydroxy- 4′H-spiro[1,3-dioxolane-2,1′-naphthalen]-4′-one) and TH-223 (5′-methoxy-4′H-spiro[1,3-dioxane-2,1′-naphthalen] -4′-one), had substantial effects on tubulin assembly and were antiproliferative at low micromolar concentrations. TH-169 was the most potent at blocking GTP-dependent polymerization of 10 μm tubulin in vitro with a remarkable 50% inhibitory concentration of ca. 400 nm. It had no effect on paclitaxel-induced microtubule assembly and did not cause microtubule hypernucleation. TH-169 failed to compete with colchicine for binding to β-tubulin. The 50% antiproliferative concentration of TH-169 against human cancer cells was at or slightly below 1 μm. Flow cytometry showed that 1 μm TH-169 caused an increase in G2/M and hypodiploid cells. TH-169 eliminated the PC-3 cells' polyploid population and increased their expression of p21WAF1 and Hsp70 in a concentration-dependent manner. The antiproliferative effect of TH-169 was irreversible and independent of changes in caspases, actin, tubulin, glyceraldehyde phosphate dehydrogenase or Bcl-xS/L. This structurally simple naphthoquinone spiroketal represents a small molecule, tubulin-interactive agent with a novel apoptotic pathway and attractive biological function. © 2008 The Authors."^^ . "2008-02-01" . . "71" . "2" . . "Chemical Biology and Drug Design"^^ . . . "17470277" . . . . . . . . . . . . . . . . . . . "TD"^^ . "Hopkins"^^ . "TD Hopkins"^^ . . "BW"^^ . "Day"^^ . "BW Day"^^ . . "CA"^^ . "Thomas"^^ . "CA Thomas"^^ . . "P"^^ . "Wipf"^^ . "P Wipf"^^ . . "R"^^ . "Balachandran"^^ . "R Balachandran"^^ . . . . . . "Tubulin-perturbing naphthoquinone spiroketals (Plain Text)"^^ . . . "licence.txt"^^ . . . "Tubulin-perturbing naphthoquinone spiroketals (Other)"^^ . . . . . . "indexcodes.txt"^^ . . "HTML Summary of #19347 \n\nTubulin-perturbing naphthoquinone spiroketals\n\n" . "text/html" . .