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

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 (IC(50): 39 and 19 μM, respectively) than camptothecin, as the positive control (IC(50): 46 μM) against topoisomerase I. Compounds, 4, 10, 12, 19, 24 and 25 showed strong inhibitory activities toward DNA topoisomerase II (IC(50): 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 (IC(50): 20 μM). In A549 cell line, 5 and 6 showed cytotoxicities (IC(50): 4 μM and 3 μM, respectively, with IC(50) of camptothecin as positive control: 10.3 μM). In the HepG2 cell line, 3, 5 and 7 showed cytotoxicity (IC(50): 4, 3 and 4 μM, respectively, with IC(50) of camptothecin: 0.3 μM). Compounds 6, 12 and 23 showed cytotoxicities in the HT-29 cell line (IC(50): 19, 19 and 15 μM, respectively, with IC(50) of camptothecin: 2 μM).

Genotoxic potential of leaf extracts of Jatropha gossypiifolia L.

“…0.00 ± 0.00 0.04 ± 0.08 0.00 ± 0.00 0.04 ± 0.08 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.47 ± 0.48 Multipolar anaphase 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.02 ± 0.06 0.00 ± 0.00 0.30 ± 0.45 Lobulated nucleus 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.00 ± 0.00 0.04 ± 0.08 0.00 ± 0. (Zheng et al, 2010), and saponins (Sánchez-Burgos et al, 2013). The probable inhibitory action on topoisomerase II by the phytochemicals of the extracts may have induced alterations in the condensation (chromosome adherence), and consequently the mitotic segregation (chromosome loss), as observed in A. cepa by Żabka et al (2014).…”

Protective constituents against sepsis in mice from the root barks of Ulmus davidiana var. japonica

“…Anticancer, antiviral, and antibacterial properties have also been reported (Jin et al, , 2008Kang et al, 2006;Suh et al, 2007). Previously, we reported anti-inflammatory activity (Zheng et al, 2010b) and topoisomerase inhibitory activity (Zheng et al, 2010a) of (-)-catechin, catechin glycosides, triterpenes, lignan, and neolignan glycosides (Lee et al, 2001;Zheng et al, 2010a) isolated from U. davidiana var. japonica.…”

Novel securinine derivatives as topoisomerase I based antitumor agents

“…All synthesized compounds were first screened for their Topo I inhibitory activity, by assessing the conversion of supercoiled pBR322 DNA to its relaxed form [22,23] in the presence of the synthetic securinine derivatives. Camptothecin (CPT), used in the clinic as a selective Topo I inhibitor, was used as positive control.…”

“…The growth inhibitory effect of securinine derivatives toward four different human cancer cell lines, A549 (adenocarcinomic human alveolar basal epithelial cell line), HeLa (human cervix tumor cell line), HepG2 (human liver tumor cell), SH-SY5Y (human neuroblastoma cell line) and L02 cell line (a healthy mammalian cell line) were assessed with a classical MTT assay [22]. The cells were plated in a density of 5 Â 10 3 per well in 96-well microplates, and incubated overnight in 100 ml of a medium containing 10% Fetal Bovine Serum (Hyclone, USA).…”

“…21.24; ESI-LRMS m/z: 382.3[MþH] þ ; ESI-HRMS m/z: 382.1652[MþH] þ , calcd for C22 H 24 NO 5 382.1649. 5.1.2.2.…”