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Inhibition of DNA topoisomerases I and II and cytotoxicity of compounds from Ulmus davidiana var. japonica

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Abstract

Twenty five compounds including ten triterpenes (1–3, 5–11), six flavonoids (12–15, 24, 25), five lignans (17, 18, 21–23), two butenyl clohexnone glycosides (19–20), one fructofuranoside (16) and one fatty acid (4) were isolated from the roots of Ulmus davidiana var. japonica. The structures of those compounds were identified by comparing their physicochemical and spectral data with those of published in literatures. All the compounds were evaluated for DNA topoisomerase inhibitory activities and cytotoxicities. Among the purified compounds, 4 and 19 showed more potent inhibitory acitivities (IC50: 39 and 19 μM, respectively) than camptothecin, as the positive control (IC50: 46 μM) against topoisomerase I. Compounds, 4, 10, 12, 19, 24 and 25 showed strong inhibitory activities toward DNA topoisomerase II (IC50: 0.1, 0.52, 0.47, 0.42, 0.17 μM and 17 nM, respectively), which were more potent than that of etoposide as positive control (IC50: 20 μM). In A549 cell line, 5 and 6 showed cytotoxicities (IC50: 4 μM and 3 μM, respectively, with IC50 of camptothecin as positive control: 10.3 μM). In the HepG2 cell line, 3, 5 and 7 showed cytotoxicity (IC50: 4, 3 and 4 μM, respectively, with IC50 of camptothecin: 0.3 μM). Compounds 6, 12 and 23 showed cytotoxicities in the HT-29 cell line (IC50: 19, 19 and 15 μM, respectively, with IC50 of camptothecin: 2 μM).

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Authors and Affiliations

  1. College of Pharmacy, Yeungnam University, Gyongsan, 712-749, Korea

    Ming Shan Zheng, Yeun-Kyung Lee, Ying Li, Kyoung Hwangbo, Hyun-Wook Chang & Jong-Keun Son

  2. Yanbian University, Yanji, 133000, China

    Ming Shan Zheng

  3. Department of Biochemistry, College of Science, Yeungnam University, Gyongsan, 712-749, Korea

    Chong-Soon Lee

  4. Department of Biochemistry and Molecular Biology, Aging-associated Vascular Disease Research Center, College of Medicine, Yeungnam University, Daegu, 705-717, Korea

    Jae-Ryong Kim

  5. Department of Pathology and Laboratory Medicine, University of California Davis, Sacramento, 95817, USA

    Sunny Kyung-Seon Lee

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  1. Ming Shan Zheng
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Zheng, M.S., Lee, YK., Li, Y. et al. Inhibition of DNA topoisomerases I and II and cytotoxicity of compounds from Ulmus davidiana var. japonica . Arch. Pharm. Res. 33, 1307–1315 (2010). https://doi.org/10.1007/s12272-010-0903-0

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