Abstract
A novel series of 4β-[(4-substituted) aroylthiourea] derivatives of podophyllotoxin were synthesized and their abilities to inhibit the growth of cancer cells were investigated by MTT assay. Compound 4a possessed the highest cytotoxicity on HepG2, A549 and HCT-116 cancer cell lines with the IC(50) values of 0.1 μM. Apoptosis in HCT-116 cells induced by compound 4a was observed by Hoechst33342-Propidium iodide (PI) and acridine orange (AO)-ethidium bromide (EB) double staining assays. DNA flow cytometric analysis revealed that 4a induced cell cycle arrest at G2/M phase and kDNA decatenation assay indicated that 4a inhibited topoisomerase IIα-mediated kDNA decatenation. Our results indicated that compound 4a possessed promising antitumor activity, which need to be studied further.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Antigens, Neoplasm / metabolism
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Antineoplastic Agents, Phytogenic / chemical synthesis*
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Antineoplastic Agents, Phytogenic / pharmacology*
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Apoptosis / drug effects
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Cell Proliferation / drug effects*
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DNA Topoisomerases, Type II / metabolism
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DNA, Catenated / metabolism
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DNA-Binding Proteins / antagonists & inhibitors
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DNA-Binding Proteins / metabolism
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Dose-Response Relationship, Drug
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Enzyme Inhibitors / chemical synthesis
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Enzyme Inhibitors / pharmacology
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Flow Cytometry
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G2 Phase Cell Cycle Checkpoints / drug effects
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HCT116 Cells
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Hep G2 Cells
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Humans
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Inhibitory Concentration 50
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M Phase Cell Cycle Checkpoints / drug effects
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Molecular Structure
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Podophyllotoxin / analogs & derivatives
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Podophyllotoxin / chemical synthesis*
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Podophyllotoxin / pharmacology*
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Staining and Labeling
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Structure-Activity Relationship
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Thiourea / analogs & derivatives
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Thiourea / chemical synthesis*
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Thiourea / pharmacology*
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Time Factors
Substances
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Antigens, Neoplasm
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Antineoplastic Agents, Phytogenic
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DNA, Catenated
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DNA-Binding Proteins
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Enzyme Inhibitors
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DNA Topoisomerases, Type II
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Thiourea
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Podophyllotoxin