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  • Title: Novel shikonin derivatives targeting tubulin as anticancer agents.
    Author: Guo J, Chen XF, Liu J, Lin HY, Han HW, Liu HC, Huang SC, Shahla BK, Kulek A, Qi JL, Wang XM, Ling LJ, Yang YH.
    Journal: Chem Biol Drug Des; 2014 Nov; 84(5):603-15. PubMed ID: 24797889.
    Abstract:
    In this study, we report the identification of a new shikonin-phenoxyacetic acid derivative, as an inhibitor of tubulin. A series of compounds were prepared; among them, compound 16 [(R)-1-(5,8-dihydroxy-1,4-dioxo-1,4-dihydronaphthalen-2-yl)-4-methylpent-3-enyl 2-(4- phenoxyphenyl) acetate] potently inhibited the function of microtubules, inducing cell growth inhibition, apoptosis of cancer cell lines in a concentration and time-dependent manner. Molecular docking involving 16 at the vinblastine binding site of tubulin indicated that a phenoxy moiety interacted with tubulin via hydrogen bonding with asparaginate (Asn) and tyrosine (Tyr). Analysis of microtubules with confocal microscopy demonstrated that 16 altered the microtubule architecture and exhibited a significant reduction in microtubule density. Cell cycle assay further proved that HepG2 cells were blocked in G2/M phase. Our study provides a new, promising compound for the development of tubulin inhibitors by proposing a new target for the anticancer activity of shikonin.
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