A series of novel C15 urushiol derivatives were designed by introducing a pechmann structure and F-, Cl-, and Br-nitro substituents with different electronic properties into its alkyl side chain, as well as a triazolyl functional group in its aromatic oxide. Their chemical structures were determined based on the analysis of the NMR (nuclear magnetic resonance) spectroscopic and mass spectrometric data. The results showed that compound exhibited a strong inhibition of the HepG2 cell proliferation (half maximal inhibitory concentration (IC50): 2.833 μM to human hepatocellular carcinoma (HepG2), and 80.905 μM to human normal hepatocytes (LO2)). Furthermore, it had an excellent synergistic effect with levopimaric acid. The nitrogen atom of the triazole ring formed a hydrogen-bonding interaction with Gly103, Gly154, and Tyr308, which made compound bind to histone deacetylase (HDAC)2 more tightly. One triazole ring and His33 formed a π⁻π stacking effect; the other, whose branches were deep into the pocket, further enhanced the interaction with HDAC2. Meanwhile, compound involved a hydrophobic interaction with the residues Phe210 and Leu276. The hydrophobic interaction and π⁻π stacking provided powerful van der Waals forces for the compounds.
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http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6214004 | PMC |
http://dx.doi.org/10.3390/ijms19103184 | DOI Listing |
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