文献类型：期刊文献

英文题名：Novel C15 Triene Triazole, D-A Derivatives Anti-HepG2, and as HDAC2 Inhibitors: A Synergy Study

作者：Qi, Zhiwen[1,2,3] Wang, Chengzhang[1,2] Jiang, Jianxin[3] Wu, Caie[4]

第一作者：Qi, Zhiwen;齐志文

通信作者：Wang, CZ[1];Wang, CZ[2]

机构：[1]China Acad Forestry, Inst Chem Ind Forest Prod, Nanjing 210042, Jiangsu, Peoples R China;[2]State Forestry Adm, Key & Open Lab Forest Chem Engn, Nanjing 210042, Jiangsu, Peoples R China;[3]Beijing Forestry Univ, Coll Mat Sci & Technol, Beijing 100083, Peoples R China;[4]Nanjing Forestry Univ, Coll Light Ind & Food Engn, Nanjing 210000, Jiangsu, Peoples R China

年份：2018

卷号：19

期号：10

外文期刊名：INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES

收录：;Scopus(收录号：2-s2.0-85055075220);WOS:【SCI-EXPANDED(收录号:WOS:000448951000339)】；

基金：This work was supported by the National Natural Science Foundation of China (31570564), the Jiangsu Provincial Key Laboratory of Biomass Energy and Materials Basic Research Business Project (JSBEM-S-201509), the Fundamental Research Funds for the Central Non-profit Research Institution of CAF (CAFYBB2018GA001), and the Introduction International Advanced Forestry Science and Technology (2015-4-46).

语种：英文

外文关键词：urushiol; triazole; diels-alder; pechmann; anti-tumor; HDAC2

摘要：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 4 exhibited a strong inhibition of the HepG2 cell proliferation (half maximal inhibitory concentration (IC50): 2.833 M to human hepatocellular carcinoma (HepG2), and 80.905 M 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 4 bind to histone deacetylase (HDAC)2 more tightly. One triazole ring and His33 formed a - stacking effect; the other, whose branches were deep into the pocket, further enhanced the interaction with HDAC2. Meanwhile, compound 4 involved a hydrophobic interaction with the residues Phe210 and Leu276. The hydrophobic interaction and - stacking provided powerful van der Waals forces for the compounds.