71835-85-3Relevant articles and documents
Synthesis of Diverse Hydroxycinnamoyl Phenylethanoid Esters Using Escherichia coli
Song, Min Kyung,Cho, A Ra,Sim, Geunyoung,Ahn, Joong-Hoon
, p. 2028 - 2035 (2019/02/26)
Caffeic acid phenethyl ester (CAPE) is an ester of a hydroxycinnamic acid (phenylpropanoid) and a phenylethanoid (2-phenylethanol; 2-PE), which has long been used in traditional medicine. Here, we synthesized 54 hydroxycinnamic acid-phenylethanoid esters by feeding 64 combinations of hydroxycinnamic acids and phenylethanols to Escherichia coli harboring the rice genes OsPMT and Os4CL. The same approach was applied for ester synthesis with caffeic acid and eight different phenyl alcohols. Two hydroxycinnamoyl phenethyl esters, p-coumaroyl tyrosol and CAPE, were also synthesized from glucose using engineered E. coli by introducing genes for the synthesis of substrates. Consequently, we synthesized approximately 393.4 mg/L p-coumaroyl tyrosol and 23.8 mg/L CAPE with this approach. Overall, these findings demonstrate that the rice PMT and 4CL proteins can be used for the synthesis of diverse hydroxycinnamoyl phenylethanoid esters owing to their promiscuity and that further exploration of the biological activities of these compounds is warranted.
Catechol-based inhibitors of bacterial urease
Pagoni, Aikaterini,Daliani, Theohari,Macegoniuk, Katarzyna,Vassiliou, Stamatia,Berlicki, ?ukasz
supporting information, p. 1085 - 1089 (2019/03/07)
Targeted covalent inhibitors of urease were developed on the basis of the catechol structure. Forty amide and ester derivatives of 3,4-dihydroxyphenylacetic acid, caffeic acid, ferulic acid and gallic acid were obtained and screened against Sporosarcinia pasteurii urease. The most active compound, namely propargyl ester of 3,4-dihydroxyphenylacetic acid exhibited IC50 = 518 nM andkinact/Ki = 1379 M?1 s?1. Inhibitory activity of this compound was better and toxicity lower than those obtained for the starting compound – catechol. The molecular modelling studies revealed a mode of binding consistent with structure-activity relationships.
Sinapic acid phenethyl ester as a potent selective 5-lipoxygenase inhibitor: Synthesis and structure–activity relationship
Touaibia, Mohamed,Hébert, Martin J. G.,Levesque, Natalie A.,Doiron, Jérémie A.,Doucet, Marco S.,Jean-Fran?ois, Jacques,Cormier, Marc,Boudreau, Luc H.,Surette, Marc E.
, p. 1876 - 1887 (2018/08/06)
Given the hepatotoxicity and an unfavorable pharmacokinetic profile of zileuton (Zyflo), currently the only approved and clinically used 5-Lipoxygenase (5-LO) inhibitor, the search for potent and safe 5-LO inhibitors is highly demanded. The action of several phenolic acid phenethyl esters as potential 5-Lipoxygenase (5-LO) inhibitors has been investigated. For this purpose, a series of 14 phenethyl esters was synthesized and their impact on 5-LO inhibition was evaluated. The effects of position and number of hydroxyl and methoxy groups on the phenolic acid were investigated. The shortening of the linker between the carbonyl and the catechol moiety as well as the presence of the α,β-unsaturated carbonyl group was also explored. The sinapic acid phenethyl ester (10), which can be named SAPE (10) by analogy to caffeic acid phenethyl ester (CAPE), inhibited 5-LO in a concentration-dependent manner and outperformed both zileuton (1) and CAPE (2). With an IC50 of 0.3?μm, SAPE (10) was threefold more potent than CAPE (2) and 10-fold more potent than zileuton (1), the only 5-LO inhibitor approved for clinical use. Unlike CAPE (2), SAPE (10) had no effect on 12-lipoxygenase (12-LO) and less effect on cyclooxygenase 1 (COX-1) which makes it a more selective 5-LO inhibitor.
Natural product-inspired esters and amides of ferulic and caffeic acid as dual inhibitors of HIV-1 reverse transcriptase
Sonar, Vijay P.,Corona, Angela,Distinto, Simona,Maccioni, Elias,Meleddu, Rita,Fois, Benedetta,Floris, Costantino,Malpure, Nilesh V.,Alcaro, Stefano,Tramontano, Enzo,Cottiglia, Filippo
, p. 248 - 260 (2017/03/09)
Using an HIV-1 Reverse Transcriptase (RT)-associated RNase H inhibition assay as lead, bioguided fractionation of the dichloromethane extract of the Ocimum sanctum leaves led to the isolation of five triterpenes (1–5) along with three 3-methoxy-4-hydroxy phenyl derivatives (6–8). The structure of this isolates were determined by 1D and 2D NMR experiments as well as ESI-MS. Tetradecyl ferulate (8) showed an interesting RNase H IC50value of 12.4?μM and due to the synthetic accessibility of this secondary metabolite, a structure-activity relationship study was carried out. A series of esters and amides of ferulic and caffeic acids were synthesized and, among all, the most active was N-oleylcaffeamide displaying a strong inhibitory activity towards both RT-associated functions, ribonuclease H and DNA polymerase. Molecular modeling studies together with Yonetani-Theorell analysis, demonstrated that N-oleylcaffeamide is able to bind both two allosteric site located one close to the NNRTI binding pocket and the other close to RNase H catalytic site.
Synthesis of caffeic acid phenethyl ester derivatives, and their cytoprotective and neuritogenic activities in PC12 cells
Shi, Haiming,Xie, Dongsheng,Yang, Ruoling,Cheng, Yaqian
, p. 5046 - 5053 (2015/04/22)
Twenty-one caffeic acid phenethyl ester (CAPE) derivatives were synthesized, and characterized by IR, HR-MS, 1H and 13C NMR analyses. All compounds were evaluated for their cytoprotective effects against H2O2-induced cytotoxicity and neuritogenic activities in the neurite outgrowth in PC12 cells. Compounds 1 and 20 exhibited stronger cytoprotective activities than their parent compound CAPE at 4 nM. Compounds 1, 4, 12 and 13 showed potential neuritogenic activities at 0.5 nM, while compounds 19 and 20 induced neurite outgrowth at 10 nM. The results from this study suggested that CAPE and its derivatives may be potential functional food ingredients for the prevention of neurodegenerative diseases.
Synthesis of caffeic acid phenethyl ester analogues and their cytotoxicities against human cancer cells
Wang, Yan-Hui,Li, Qu-Sheng,Wang, Peng-Long,Xu, Kuo,Cheng, Ya-Tao,Xu, Xin,Li, Qiang,Zhang, Yu-Zhong,Lei, Hai-Min
, p. 2686 - 2690 (2014/06/09)
Although caffeic acid phenethyl ester exhibits strong antitumor property, but its pharmacophore has not been elaborated clearly as yet. Seventeen caffeic acid phenethyl ester analogues were synthesized via simple and easy procedures and their antiprolifer
Induction of adiponectin by natural and synthetic phenolamides in mouse and human preadipocytes and its enhancement by docosahexaenoic acid
Yamazaki, Yoshimitsu,Kawano, Yasuhiro,Uebayasi, Masami
, p. 290 - 300 (2008/09/16)
Adiponectin, the adipose-derived cytokine, plays an important role in preventing metabolic syndromes. To develop new adiponectin inducers, eight species of ferulic esters and amides, and five related compounds were synthesized and tested on the stimulation of adiponectin production in mouse 3T3-L1 and normal human preadipocytes. The ferulamides with an aromatic ring in the N-substituent are very active in inducing adiponectin as compared with the known active compounds, curcumin, [6]-gingerol, and capsaicin, and furthermore the activities of these ferulamides are remarkably stronger than those of the corresponding esters or the straight chain octylamide. The most active compound, N-(2-phenylethyl)ferulamide (7), was found to activate the PPAR (peroxisome proliferator-activated receptor) γ-RXR (retinoid X receptor) α heterodimeric complex in the PPRE (PPAR-responsive element)-driven luciferase reporter assay. The adiponectin production by 7 is synergistically enhanced by coaddition of a PPARγ-specific agonist, pioglitazone (PGZ), or another PPARγ agonist, docosahexaenoic acid (DHA), in cultured preadipocytes. The compound 7 alone did not show a statistically significant effect on the plasma adiponectin level in KK-Ay/Ta mice, while 1% 7 in the diets significantly lowered the blood glucose and triglyceride levels and 0.3% 7 mixed with DHA oil in the diets significantly increased the adiponectin level as compared with the control. These results suggest that the present ferulamides would be useful lead compounds in developing more potent agents for treatment of metabolic syndromes through promoting the endogenous adiponectin production, and that such an activity is possibly enhanced by the coadministration with DHA.
Hydroxylated aromatic inhibitors of HIV-1 integrase
Burke Jr.,Fesen,Mazumder,Wang,Carothers,Grunberger,Driscoll,Kohn,Pommier
, p. 4171 - 4178 (2007/10/03)
Efficient replication of HIV-1 requires integration of a DNA copy of the viral genome into a chromosome of the host cell. Integration is catalyzed by the viral integrase, and we have previously reported that phenolic moieties in compounds such as flavones, caffeic acid phenethyl ester (CAPE, 2), and curcumin confer inhibitory activity against HIV-1 integrase. We now extend these findings by performing a comprehensive structure-activity relationship using CAPE analogues. Approximately 30 compounds have been prepared as HIV integrase inhibitors based on the structural lead provided by CAPE, which has previously been shown to exhibit an IC50 value of 7 μM in our integration assay. These analogues were designed to examine specific features of the parent CAPE structure which may be important for activity. Among the features examined for their effects on inhibitory potency were ring substitution, side chain length and composition, and phenyl ring conformational orientation. In an assay which measured the combined effect of two sequential steps, dinucleotide cleavage and strand transfer, several analogues have IC50 values for 3'-processing and strand transfer lower than those of CAPE. Inhibition of strand transfer was assayed using both blunt-ended and 'precleaved' DNA substrates. Disintegration using an integrase mutant lacking the N-terminal zinc finger and C-terminal DNA-binding domains was also inhibited by these analogues, suggesting that the binding site for these compounds resides in the central catalytic core. Several CAPE analogues were also tested for selective activity against transformed cells. Taken together, these results suggest that the development of novel antiviral agents for the treatment of acquired immune deficiency syndrome can be based upon inhibition of HIV-1 integrase.
