title: Synthesis and bioevaluation of diphyllin glycosides as novel anticancer agents.
abstract: A series of diphyllin glycosides were synthesized from diphyllin by phase transfer catalysis glycosylation, deprotection, and etherification, and the structures were established by (1) H NMR, (13) C NMR, and HRMS. These glycosides were evaluated for their in vitro cytotoxicity against HCT-116, A549, and A549T cancer cell lines by MTT assay, and most of them were cytotoxic at submicromolar concentrations. They were also effective against the paclitaxel-resistant cell line A549T. The kDNA decatenation assay indicated that most of these compounds inhibited topoisomerase IIα-mediated kDNA decatenation. In addition, the in vitro tubulin polymerization study showed that compounds 5 and 6 had antimicrotubule activity with a paclitaxel-like mode of action. Taken together, these results suggest that these diphyllin glycosides act on both TopoII and tubulin.
authors.affiliation: Institute of Nautical Medicine, Nantong University, Nantong, People's Republic of China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhao
authors.forename: Chunyan
authors.initials: C
authors.lastname: Ni
authors.forename: Yuting
authors.initials: Y
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhu
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D052117:Benzodioxoles; D001921:Brain / Q000187:drug effects / Q000378:metabolism; D045744:Cell Line, Tumor; D004148:Dioxolanes / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor / Q000379:methods / Q000706:statistics & numerical data; D006027:Glycosides / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D020128:Inhibitory Concentration 50; D017705:Lignans / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D059005:Topoisomerase II Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D014404:Tubulin / Q000819:agonists / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D052117:Benzodioxoles; D004148:Dioxolanes; D006027:Glycosides; D017705:Lignans; D059005:Topoisomerase II Inhibitors; D014404:Tubulin; C010130:diphyllin