155997-94-7Relevant academic research and scientific papers
Novel drug isolated from mistletoe (1: E,4 E)-1,7-bis(4-hydroxyphenyl)hepta-1,4-dien-3-one for potential treatment of various cancers: Synthesis, pharmacokinetics and pharmacodynamics
Hong, Jing,Meng, Lin,Qin, Feng,Yu, Peipei,Yu, Zhiguo,Zhang, Zhaoyan,Zhao, Yunli,Zhou, Ceng
, p. 27794 - 27804 (2020)
(1E,4E)-1,7-Bis(4-hydroxyphenyl)hepta-1,4-dien-3-one (DHDK) is a novel curcuminoid analogue isolated from mistletoe. DHDK exhibits better anti-tumour activity, higher bioavailability and superior stability than curcumin. DHDK is difficult to isolate from Viscum coloratum, but it can be synthesised. MTT (methylthiazolyldiphenyl tetrazolium bromide) assay was used to evaluate the in vitro cytotoxic activity of synthesised DHDK on 12 cancer cell lines. Results showed that DHDK exhibited excellent potential as an anticancer agent, especially for breast and lung cancer. Efficacy was further evaluated in vivo by using MCF-7 breast cancer models. DHDK showed a dose-dependent relationship without weight reduction, mortality growth inhibition or tissue toxicity. Pharmacokinetics and tissue distribution statistics were determined by LC-ESI-MS/MS. This work provided preliminary data on this natural compound and could open up new prospects for changing related parameters to improve drug efficacy.
Method for synthesizing 1, 7-2-(4-hydroxy phenyl)-heptane-1, 4-diene-3-ketone
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, (2018/04/03)
The invention relates to the field of pharmaceutical synthesis, in particular to a method for synthesizing 1,7-2-(4-hydroxy phenyl)-heptane-1,4-diene-3-ketone. The method, selecting 3-(4- hydroxy phenyl)propionic acid and 4-hydroxybenzaldehyde as raw materials, includes (1), subjecting the 3-(4-hydroxy phenyl)propionic acid to esterification, methyl protection, reduction and oxidation to obtain 3-(4-(methoxy methyl)phenyl)propionaldehyde; (2), subjecting the 4-hydroxybenzaldehyde to etherification and aldol reaction to obtain 4-(4-((methoxy methyl)phenyl)butyl-3-alkene-2-ketone; (3), subjecting the 4-(4-((methoxy methyl)phenyl) butyl-3-alkene-2-ketone and the 3-(4-(methoxy methyl)phenyl)propionaldehyde to aldol condensation, and allowing the reactor to react with hydrochloric acid to obtain 1, 7-2-(4-hydroxy phenyl)-heptane-1,4-diene-3-ketone. The method has the advantages of simplicity, easiness in operation, high yield and high purity.
Synthesis and protein kinase C inhibitory activities of acyclic balanol analogs that are highly selective for protein kinase C over protein kinase A
Defauw, Jean M.,Murphy, Marcia M.,Jagdmann Jr., G. Erik,Hu, Hong,Lampe, John W.,Hollinshead, Sean P.,Mitchell, Thomas J.,Crane, Heidi M.,Heerding, Julia M.,Mendoza, José S.,Davis, Jefferson E.,Darges, James W.,Hubbard, Frederick R.,Hall, Steven E.
, p. 5215 - 5227 (2007/10/03)
A series of balanol analogs in which the perhydroazepine ring and the p- hydroxybenzamide moiety were combined into an acyclic linked unit have been prepared and evaluated for their inhibitory properties against the serine/threonine kinase PKC. Several low-micromolar to lownanomolar inhibitors of the α, β'(I), β(II), γ, δ, ε, and η PKC isozymes were prepared. In general, these acyclic balanol analogs were found to be highly selective for PKC over the serine/threonine kinase PKA. The type and number of atoms linking the benzophenone ester to the p-hydroxyphenyl group necessary for optimal PKC inhibition were investigated. The most potent compounds contained a three-carbon linker in which the carboxamide moiety of balanol had been replaced by a methylene group. The effect of placing substituents on the three-carbon chain was also investigated. The preferred compounds contained either a 2-benzene-sulfonamido (6b) or a 1-methyl (21b) substituent. The preferred compounds 6b and 21b were tested against a panel of serine/threonine kinases and found to be highly selective for PKC. The more active enantiomer of 6b, (S)-12b, was 3-10-fold more active than the R- enantiomer against the PKC isozymes. The effect of making the analogs more rigid by making the three-carbon chain part of a five-membered ring, but with retention of the methylene replacement for the carboxamide moiety, led to potent PKC inhibitors including anti-substituted pyrrolidine analog 35b and the most potent PKC inhibitor in the series, anti-substituted cyclopentane analog 29b. The anti cyclopentane analog 29b was a low-micromolar inhibitor of the PMA-induced superoxide burst in neutrophils, and its carboxylic ester was a high-nanomolar inhibitor of neutrophils. Finally esterification of 21b, (S)-12b, and 35b turned these potent PKC inhibitors into low-micromolar inhibitors of neutrophils.
Protecting group for carboxyl function: Mild and facile cleavage of 2- cyanoethyl ester under non-hydrolytic conditions
Kita,Maeda,Takahashi,Fukui,Ogawa,Hatayama
, p. 147 - 150 (2007/10/02)
The use of the 2-cyanoethyl group for carboxyl-protection is described. This group was readily introduced by esterification using ethylene cyanohydrin and the deprotection was carried out under mild conditions using tetrabutylammonium fluoride in dimethylformamide-tetrahydrofuran.
