Based on the use of quercetin for treating diabetes and H 2 S for promoting wound healing, a series of three quercetin-linker-H 2 S donor conjugates was designed, synthesized and characterized by 1 H-NMR, 13 C-NMR and MS. Meanwhile, in vitro evaluation of these compounds was also researched by IR-HepG2 treatment experiment, MTT assay, scratch test and tubule formation experiment. The three compounds could be used to treat insulin resistance induced by high glucose and promote the proliferation of human umbilical vein endothelial cells, wound healing, and the formation of tubules in vitro under a highglucose environment. Our results illustrate that these compounds could be used to treat diabetes and promote wound healing at the same time. Furthermore, molecular docking study results of the compounds were consistent with the evaluated biological activity. In vivo research of compounds is underway.
In this work, a series of 7-azaindole analogs were designed by the bioisosteric principle based on the pharmacodynamic parent nucleus. Moreover,pyridin-3-yl)methyl]-N-{[6-(trifluoromethyl)pyridin-3-yl]methyl}pyrimidin-2-amine (compound P1) with the strongest interaction with colony-stimulating factor 1 receptor (CSF-1R) was screened by molecular docking. Compound P1 was successfully prepared by the six-step reaction with HPLC purity of 99.26 % and characterized by 1 H-NMR and ESI-MS spectra. In vitro bioactivity study showed that compound P1 appeared the cytotoxicity to MCF-7 and A549 cells, especially to HOS cells (IC 50 = 88.79 � 8.07 nM), while it had lower toxicity to normal L929 cells (IC 50 = 140.49 � 8.03 μM). In addition, compound P1 could induce HOS cell death by apoptosis and blocking the G0/G1 phase at nanomolar concentrations. The obtained results indicated that compound P1 might be a promising candidate compound for anticancer drug.
Background:
Novel anti-tumor bioactivity compounds were designed by the strategy of modular hybridization with the bioactivity advantages of 5-fluorouracil and dithiocarbamate derivatives.
Methods:
A series of novel 5-fluorouracil-dithiocarbamate conjugates were synthesized, characterized and evaluated for their cytotoxic activities in vitro against B16, Hela and U87MG by MTT assay. Colony-formation, transwell migration, cell apoptosis and cell cycle distribution assays were performed to explore the anti-tumor activities and mechanism of conjugates for compounds P3 and P4. Conjugates, dithiocarbamate derivatives combined with copper ions and 5-fluorouracil were investigated by molecular docking.
Results:
The results of cytotoxicity assays illuminated that these conjugates had anti-tumor activity against B16, Hela and U87MG. Interestingly, the cytotoxicity of these conjugates was significantly increased when combined with copper ions, and compound P3 displayed better bioactivity compared to the other compounds. Conjugates might be metabolized in the cells to produce dithiocarbamates, and then metabolites formed complexes with copper ions, generating better anti-tumor effects. Molecular docking studies exhibited that compound P3 appeared the strongest interaction with the receptors 6CCY and 5T92.
Conclusion:
Compound P3 exhibited better anti-tumor bioactivity and might be emerged as the lead compound for the treatment of glioma. Further research in vivo will be performed in our following work.
result:
The results of cytotoxicity assays illuminated that these conjugates had anti-tumor activity against B16, Hela and U87MG. Interestingly, the cytotoxicity of these conjugates was significantly increased when combined with copper ions and compound P3 displayed better bioactivity compared to the other compounds. Conjugates might be metabolized in the cells to produce dithiocarbamates, then metabolites formed complexes with copper ions, generating better anti-tumor effects. Molecular docking studies exhibited that compound P3 appeared the strongest interaction with the receptors 6CCY and 5T92.
other:
None
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