- β-Carboline and N-hydroxycinnamamide hybrids as anticancer agents for drug-resistant hepatocellular carcinoma
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In an effort to develop anticancer agents that may overcome drug resistance, the number one reason in caner death, we have developed a series of novel hybrids of β-carboline and N-hydroxycinnamamide as histone deacetylase (HDAC) inhibitors. Most of the hybrids 13a-p showed strong antiproliferative effects with low-micromolar IC50 values against four human cancer cells. The most potent compound of series 13p exhibited high HDAC1/6 inhibitory effects, and also increased the acetylation levels of histone H3, H4 and α-tubulin. Importantly, 13p demonstrated high anticancer potency against drug-sensitive HepG2 and Bel7402 cells and drug-resistant Bel7402/5FU cells. Hybrid 13p triggered significant apoptosis by regulating apoptotic relative proteins expression in these Bel7402/5FU cells. Finally, 13p induced a substantial amount of autophagic flux activity by the accretion of the expression of LC3-II and the degeneration of expression of p62 and LC3-I in Bel7402/5FU cells. Overall, 13p is a novel β-carboline/N-hydroxycinnamamide hybrid with significant anticancer potency that warrants further evaluation for the treatment of drug-resistant hepatocellular carcinoma.
- Ling, Yong,Gao, Wei-Jie,Ling, Changchun,Liu, Ji,Meng, Chi,Qian, Jianqiang,Liu, Siqun,Gan, Huiling,Wu, Hongmei,Tao, Jinhua,Dai, Hong,Zhang, Yanan
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p. 515 - 526
(2019/03/08)
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- Synthesis method of ozagrel intermediate phenol bromomethyl cinnamate
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The invention discloses a synthesis method of bromomethyl cinnamate by uisng an ozagrel intermediate, which is characterized in that the p-bromomethyl cinnamate is brominated to obtain phenol bromomethyl cinnamate, and the reaction process comprises the following steps of: 1) under the condition of protective gas, uniformly mixing the p-bromomethyl cinnamate, an auxiliary substance and a solvent A, controlling the reaction temperature to be 110-130 DEG C and the pressure to be 4-6 atmospheric pressures, stirring for 1-2h, maintaining the reaction conditions, starting to drop a mixed aqueous solution C of brominated salt and glacial acetic acid, controlling the dropping time to be 1-3 hours, controlling the temperature to be 140-160 DEG C after dropping, controlling the pressure to be 7-10-10 atmospheric pressures, and finishing the reaction after 4-6 hours; 2) cooling the system, pouring the reaction product into 2-4 times of volume of water, adding a solvent B for extraction, layering, washing an organic layer by water, drying by a drying agent, and concentrating and evaporating to remove the solvent to obtain the product. The synthesis method has the advantages of good selectivity, low cost and high yield.
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Paragraph 0027-0032; 0039-0054
(2019/06/27)
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- The Determination of Inductive Effects by 13C Nuclear Magnetic Resonance Spectrometry
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A series of meta- and para-XCH2-substituted methyl cinnamates has been prepared and the 13C n.m.r. chemical shifts of the α- and β-side-chain carbons have been determined in ethanol.In the majority of cases the magnitudes of the substituent-induced chemic
- Happer, Duncan A. R.,Steenson, Bruce E.
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p. 843 - 848
(2007/10/02)
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