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OBJECTIVE To design and synthesize a series of bifunctional ruthenium complexes containing hydroxamic acid as HDAC6 selective inhibitors by conjugating aromatic hydroxamic acid with bipyridine ruthenium (Ⅱ) complexes, and investigate the in vitro antitumor activity. METHODS Three ruthenium complexes were synthesized with aromatic ring as ‘Linker’ and hydroxamic acid as zinc binding group(ZBG), and their structures were characterized by 1H-NMR, 13C-NMR and HRMS spectrometry. The HDAC inhibitory activity was evaluated by fluorescence analysis. The in vitro antitumor activities against A549, MDA-MB-231, MCF-7, HepG-2 and LO2 cell lines were evaluated by MTT assay. The binding of compounds to the active site of HDAC6 protein was studied by molecular docking. RESULTS All compounds showed selective HDAC6 inhibitory effect, in vitro antitumor activity and tumor-targeting activity, among which representative compound 3 exhibited comparable cytotoxic activity to cisplatin and much higher tumor-targeting activity than cisplatin. CONCLUSION The introduction of a wider “Cap” (surface recognition unit) in the pharmacophore model can improve the specific recognition of the compound against HDAC6, which proved that the design of bifunctional aromatic hydroxamic acid and bipyridine ruthenium complexes is rational.
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| 科 Family | 属数 Number of genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) | 属 Genus | 种数 Number of species | 占总种数比例 Percentage of total species (%) |
|---|---|---|---|---|---|---|
| 鹅膏菌科Amanitaceae | 2 | 11 | 5.26 | 鹅膏菌属 Amanita | 10 | 4.78 |
| 小菇科 Mycenaceae | 2 | 12 | 5.74 | 丝盖伞属 Inocybe | 5 | 2.39 |
| 多孔菌科 Polyporaceae | 8 | 14 | 6.70 | 蜡蘑属 Laccaria | 5 | 2.39 |
| 红菇科 Russulaceae | 3 | 23 | 11.00 | 小皮伞属 Marasmius | 6 | 2.87 |
| 小菇属 Mycena | 11 | 5.26 | ||||
| 光柄菇属 Pluteus | 5 | 2.39 | ||||
| 红菇属 Russula | 17 | 8.13 | ||||
| 栓菌属 Trametes | 5 | 2.39 |
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