Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-07 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To improve the water solubility and biological activity of neoligans (magnolol and honokiol) and test the antitumor activity of the modified compounds. Methods The glycosylated products of magnolol and honokiol were obtained by enzymatic synthesis using a UDP-glycosyltransferase (YjiC) from Bacillus. The products were characterized by high-performance liquid chromatography (HPLC), liquid chromatography-mass spectrometry (LC-MS), and nuclear magnetic resonance (NMR) analysis. MTT assay was used to detect the growth inhibition of 4 human cancer cell lines induced by the compounds. Results We obtained two glucosides of neolignans (magnolol and honokiol) for the first time by enzymatic synthesis using a UDP-glycosyltransferase. Based on the spectroscopic data, the glucosides were identified as magnolol-2- O-β-D-glucopyranoside (1) and honokiol-4'-O-β-D-glucopyranoside (2). Compounds 1-4 exhibited moderate anti-proliferative activities against the 4 human cancer cell lines, with IC 50 values ranging from 9.41 to 111.21 µmol/L. Conclusion The glycoslated products show enhanced water solubility and drug sensitivity against SMMC7721 cells, suggesting their value as potential therapeutic drugs.
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2017-12-07 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To explore the effect of the Hsp90 inhibitor anacardic acid on cell proliferation, invasion and migration of breast cancer MDA-MB-231 cells. Methods The inhibitory effect of anacardic acid on Hsp90 was assessed with in vitro ATPase inhibition assay and ATP-sepharose binding assay. MTT assay was used to detect the growth inhibition induced by anacardic acid in MDA-MB-231 cells. Transwell assays were used to evaluate MDA-MB-231 cell invasion and migration. Western blotting was performed to assess the effect of anacardic acid in triggering the degradation of MMP-9, TIMP-1, Hsp90, and Hsp70. Results Anacardic acid exhibited a modest activity of ATPase inhibition with an IC50 value of 82.5μmol/L. Anacardic acid significantly suppressed the proliferation of MDA-MB-231 cells in a dose-dependent manner (IC50 value of 29.3μmol/L). Treatment with 12.5, 25, and 50 }mol儿anacardic acid for 36 h caused inhibition of cell invasion by 23.6%, 56.6%, and 67.0% in MDA-MB-231 cells, respectively (P<0.05), and anacardic acid treatment for 24 h inhibited the cell migration by 30.0%, 45.5% and 77.5%, respectively (P<0.05). Anacardic acid dose-dependently induced MMP-9 degradation, but did not obviously affect Hsp90 or Hsp70 expressions. Conclusion Anacardic acid can significantly inhibit the proliferation, invasion, and migration of MDA-MB-231 cells, the mechanism of which may involve the inhibition of Hsp90 ATPse activity and down-regulation of MMP-9 expression.
Subjects: Medicine, Pharmacy >> Preclinical Medicine submitted time 2018-01-25 Cooperative journals: 《南方医科大学学报》
Abstract： Objective To modify the structure of psoralidin using in vitro enzymatic glycosylation to improve its water solubilityand stability. Methods A new psoralidin glucoside (1) was obtained by enzymatic glycosylation using a UDP-glycosyltransferase. The chemical structure of compound 1 was elucidated by HR-ESI-MS and nuclear magnetic resonance(NMR) analysis. The high-performance liquid chromatography (HPLC) peaks were integrated and sample solution concentrations were calculated. MTT assay was used to detect the cytotoxicity of the compounds against 3 cancer cell lines in vitro. Results Based on the spectroscopic data, the new psoralidin glucoside was identified as psoralidin-6',7-di-O glucopyranoside (1), whose water solubility was 32.6-fold higher than that of the substrate. Analyses of pH and temperature stability demonstrated that compound 1 was more stable than psoralidin at pH 8.8 and at high temperatures. Only psoralidin exhibited a moderate cytotoxicity against 3 human cancer cell lines. Conclusion In vitro enzymatic glycosylation is a powerful approach for structural modification and improving water solubility and stability of compounds.
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