ABSTRACT
Objective: To synthesize metal complexes of Au(III) with matrine (MT-Au) and oxymatrine (OMT-Au), compare their inhibitory effect on the proliferation of tumor cells in vitro, and discuss the mechanism and structure-activity relationship. Methods: The metal complexes were synthesized by solvothermal method and characterized by X-ray single crystal diffraction. The in vitro cytotoxicity of complexes with different doses towards 10 selected tumor cell lines was evaluated by MTT method. The effects of complex on cell apoptosis and cell cycle were investigated by flow cytometer. Agarose gel electrophoresis was used to study the effects of complex on topoisomerase I (TOPO I) activity. Results: Complex OMT-Au obviously inhibited the proliferation of MGC803 tumor cells, blocked cell cycle of MGC803 in G2/M phase, and suppressed TOPO I mediated untwisting of pUC19 DNA plasmid with a dose-dependence manner. And the inhibited effects of complex OMT-Au were all stronger than MT-Au complex. Conclusion: The antitumor activity of complex OMT-Au is stronger than that of MT-Au, which could be attributed to the variation in the molecular conformation of ligand.
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OBJECTIVE: To study the synthesis and antitumor activity of novel quinolone derivatives. METHODS: Based on the structure of ciprofloxacin, the objective substances were designed and synthesized according to the principle of fragmentbased drug discovery. Their anti-tumor activities in vitro were evaluated against A549, HL-60, and Hela cells by MTT assay. Molecular docking studies were performed with the Libdock protocol of Discovery Studio to afford the ideal interaction mode of the compound with the binding site of the Topo I. RESULTS: Eight novel compounds were synthesized and showed potential antitumor activities. CONCLUSION: The antitumor activities of the synthesized quinolone derivatives are worthy of further study.
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OBJECTIVE: To synthesize quinolone derivatives and investigate their anti-tumor activities in vitro. METHODS: A series of quinolone derivatives were designed and synthesized from Norfloxacin or Ciprofloxacin with N-(phenylsulfonyl) formimidamide. Their anti-tumor activities in vitro were evaluated for A549, HL-60, Hela cells by MTT assay. Molecular docking studies were performed with the Discovery Studio to afford the ideal interaction mode of the compound into the binding site of the Topo I. RESULTS: Fourteen novel compounds were synthesized and the structures were characterized by H-NMR, ESI and HRMS. MTT assay showed that most quinolone derivatives exhibited some anti-tumor activities. CONCLUSION: These quinolone derivatives are worth further being developed.
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OBJECTIVE: To formulate the three-dimensional quantitative structure-activity relationship (3D-QSAR) model of 23-hydroxybetulinic acid derivatives with promising antitumor activity and study their molecular docking with topoisomerase I (Topo I).