709007-50-1Relevant articles and documents
5-Hydroxyferulic acid methyl ester isolated from wasabi leaves inhibits 3T3-L1 adipocyte differentiation
Misawa, Naoki,Hosoya, Takahiro,Yoshida, Shuhei,Sugimoto, Osamu,Yamada-Kato, Tomoe,Kumazawa, Shigenori
, p. 1304 - 1310 (2018/03/01)
To investigate the compounds present in wasabi leaves (Wasabia japonica Matsumura) that inhibit the adipocyte differentiation, activity-guided fractionation was performed on these leaves. 5-Hydroxyferulic acid methyl ester (1: 5-HFA ester), one of the phenylpropanoids, was isolated from wasabi leaves as a compound that inhibits the adipocyte differentiation. Compound 1 suppressed the intracellular lipid accumulation of 3T3-L1 cells without significant cytotoxicity. Gene expression analysis revealed that 1 suppressed the mRNA expression of 2 master regulators of adipocyte differentiation, PPARγ and C/EBPα. Furthermore, 1 downregulated the expression of adipogenesis-related genes, GLUT4, LPL, SREBP-1c, ACC, and FAS. Protein expression analysis revealed that 1 suppressed PPARγ protein expression. Moreover, to investigate the relationship between the structure and activity of inhibiting the adipocyte differentiation, we synthesized 12 kinds of phenylpropanoid analog. Comparison of the activity among 1 and its analogs suggested that the compound containing the substructure that possess a common functional group at the ortho position such as a catechol group exhibits the activity of inhibiting the adipocyte differentiation. Taken together, our findings suggest that 1 from wasabi leaves inhibits adipocyte differentiation via the downregulation of PPARγ.
Semi-synthesis and Structure–Activity Relationship of Neuritogenic Oleanene Derivatives
Bian, Linglin,Cao, Shining,Cheng, Lihong,Nakazaki, Atsuo,Nishikawa, Toshio,Qi, Jianhua
supporting information, p. 1972 - 1977 (2018/09/06)
(3S,4R)-23,28-Dihydroxyolean-12-en-3-yl (2E)-3-(3,4-dihydroxyphenyl)acrylate (1 a), which possesses significant neuritogenic activity, was isolated from the traditional Chinese medicine (TCM) plant, Desmodium sambuense. To confirm the structure and to assess biological activity, we semi-synthesized 1 a from commercially available oleanolic acid. A series of novel 1 a derivatives was then designed and synthesized for a structure–activity relationship (SAR) study. All synthetic derivatives were characterized by analysis of spectral data, and their neuritogenic activities were evaluated in assays with PC12 cells. The SAR results indicate that the number and position of the hydroxy groups on the phenyl ring and the triterpene moiety, as well as the length of the (saturated or unsaturated) alkyl chain that links the phenyl ring with the triterpene critically influence neuritogenic activity. Among all the tested compounds, 1 e [(3S,4R)-23,28-dihydroxyolean-12-en-3-yl (2E)-3-(3,4,5-trihydroxyphenyl)acrylate] was found to be the most potent, inducing significant neurite outgrowth at 1 μm.
p-Hydroxyphenylacetate 3-Hydroxylase as a Biocatalyst for the Synthesis of Trihydroxyphenolic Acids
Dhammaraj, Taweesak,Phintha, Aisaraphon,Pinthong, Chatchadaporn,Medhanavyn, Dheeradhach,Tinikul, Ruchanok,Chenprakhon, Pirom,Sucharitakul, Jeerus,Vardhanabhuti, Nontima,Jiarpinitnun, Chutima,Chaiyen, Pimchai
, p. 4492 - 4502 (2015/08/18)
Trihydroxyphenolic acids such as 3,4,5-trihydroxycinnamic acid (3,4,5-THCA) 4c and 2-(3,4,5-trihydroxyphenyl)acetic acid (3,4,5-THPA) 2c are strong antioxidants that are potentially useful as medicinal agents. Our results show that p-hydroxyphenylacetate (HPA) 3-hydroxylase (HPAH) from Acinetobacter baumannii can catalyze the syntheses of 3,4,5-THPA 2c and 3,4,5-THCA 4c from 4-HPA 2a and p-coumaric acid 4a, respectively. The wild-type HPAH can convert 4-HPA 2a completely into 3,4,5-THPA 2c within 100 min (total turnover number (TTN) of 100). However, the wild-type enzyme cannot efficiently synthesize 3,4,5-THCA 4c. To improve the efficiency, the oxygenase component of HPAH (C2) was rationally engineered in order to maximize the conversion of p-coumaric acid 4a to 3,4,5-THCA 4c. Results from site-directed mutagenesis studies showed that Y398S is significantly more effective than the wild-type enzyme for the synthesis of 3,4,5-THCA 4c; it can catalyze the complete bioconversion of p-coumaric acid 4a to 3,4,5-THCA 4c within 180 min (TTN ～ 23 at 180 min). The yield and stability of 3,4,5-THPA 2c and 3,4,5-THCA 4c were significantly improved in the presence of ascorbic acid. Thermostability studies showed that the wild-type C2 was very stable and remained active after incubation at 30, 35, and 40 °C for 24 h. Y398S was moderately stable because its activity was retained for 24 h at 30 °C and for 15 h at 35 °C. Transient kinetic studies using stopped-flow spectrophotometry indicated that the key improvement in the reaction of Y398S with p-coumaric acid 4a lies within the protein-ligand interaction. Y398S binds to p-coumaric acid 4a with higher affinity than the wild-type enzyme, resulting in a shift in equilibrium toward favoring the productive coupling path instead of the path leading to wasteful flavin oxidation.
Biology-oriented development of novel lipophilic antioxidants with neuroprotective activity
Silva,Bravo,Summavielle,Remio,Prez,Gil,Martnez,Borges
, p. 15800 - 15811 (2015/03/04)
Hydroxycinnamic derivatives based on ferulic and caffeic acids were designed to meet the pharmacokinetic requirements to cross the blood-brain barrier and to display neuroprotective activity within the central nervous system. Biological screening included
Novel flavonol glycosides from the aerial parts of lentil (Lens culinaris)
Zuchowski, Jerzy,Pecio, Lukasz,Stochmal, Anna
, p. 18152 - 18178 (2015/02/19)
While the phytochemical composition of lentil (Lens culinaris) seeds is well described in scientific literature, there is very little available data about secondary metabolites from lentil leaves and stems. Our research reveals that the aerial parts of lentil are a rich source of flavonoids. Six kaempferol and twelve quercetin glycosides were isolated, their structures were elucidated using NMR spectroscopy and chemical methods. This group includes 16 compounds which have not been previously described in the scientific literature: quercetin 3-O-P-D-glucopyranosyl(1→2)-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (1), kaempferol 3-O-β-D-glucopyranosyl(1→2)-β-D-galactopyranoside-7-O-β-D-glucuropyranoside (3), their derivatives 4-10,12-15,17,18 acylated with caffeic, p-coumaric, ferulic, or 3,4,5-trihydroxycinnamic acid and kaempferol 3-O-{[(6-O-E - p-coumaroyl)-β-D-glucopyranosyl(1→2)]-α-L-rhamnopyranosyl(1-6)}-β-D-galactopyranoside-7-O-α-L-rhamnopyranoside (11). Their DPPH scavenging activity was also evaluated. This is probably the first detailed description of flavonoids from the aerial parts of lentil.
Exploring nature profits: Development of novel and potent lipophilic antioxidants based on galloyl-cinnamic hybrids
Teixeira, Jose,Silva, Tiago,Benfeito, Sofia,Gaspar, Alexandra,Garrido, E. Manuela,Garrido, Jorge,Borges, Fernanda
, p. 289 - 296 (2013/05/22)
Phenolic acids are ubiquitous antioxidants accounting for approximately one third of the phenolic compounds in our diet. Their importance was supported by epidemiological studies that suggest an inverse relationship between dietary intake of phenolic antioxidants and the occurrence of diseases, such as cancer and neurodegenerative disorders. However, until now, most of natural antioxidants have limited therapeutic success a fact that could be related with their limited distribution throughout the body and with the inherent difficulties to attain the target sites. The development of phenolic antioxidants based on a hybrid concept and structurally based on natural hydroxybenzoic (gallic acid) and hydroxycinnamic (caffeic acid) scaffolds seems to be a suitable solution to surpass the mentioned drawbacks. Galloyl-cinnamic hybrids were synthesized and their antioxidant activity as well as partition coefficients and redox potentials evaluated. The structure-property-activity relationship (SPAR) study revealed the existence of a correlation between the redox potentials and antioxidant activity. The galloyl-cinnamic acid hybrid stands out as the best antioxidant supplementing the effect of a blend of gallic acid plus caffeic acid endorsing the hypothesis that the whole is greater than the sum of the parts. In addition, some hybrid compounds possess an appropriate lipophilicity allowing their application as chain-breaking antioxidant in biomembranes or other type of lipidic systems. Their predicted ADME properties are also in accordance with the general requirements for drug-like compounds. Accordingly, these phenolic hybrids can be seen as potential antioxidants for tackling the oxidative status linked to the neurodegenerative, inflammatory or cancer processes.
Contribution of cinnamic acid analogues in rosmarinic acid to inhibition of snake venom induced hemorrhage
Aung, Hnin Thanda,Furukawa, Tadashi,Nikai, Toshiaki,Niwa, Masatake,Takaya, Yoshiaki
experimental part, p. 2392 - 2396 (2011/05/12)
In our previous paper, we reported that rosmarinic acid (1) of Argusia argentea could neutralize snake venom induced hemorrhagic action. Rosmarinic acid (1) consists of two phenylpropanoids: caffeic acid (2) and 3-(3,4-dihydroxyphenyl)lactic acid (3). In this study, we investigated the structural requirements necessary for inhibition of snake venom activity through the use of compounds, which are structurally related to rosmarinic acid (1). By examining anti-hemorrhagic activity of cinnamic acid analogs against Protobothrops flavoviridis (Habu) venom, it was revealed that the presence of the E-enoic acid moiety (-CHCH-COOH) was critical. Furthermore, among the compound tested, it was concluded that rosmarinic acid (1) (IC50 0.15 μM) was the most potent inhibitor against the venom.
Antioxidant versus cytotoxic properties of hydroxycinnamic acid derivatives - A new paradigm in phenolic research
Esteves, Mario,Siquet, Christophe,Gaspar, Alexandra,Rio, Vitor,Sousa, Joana B.,Reis, Salette,Marques, Maria P. M.,Borges, Fernanda
experimental part, p. 164 - 173 (2009/04/04)
Trihydroxycinnamic derivatives were synthesized and evaluated for their antioxidant and cytotoxic activities. The ester derivatives exhibited a higher radical-scavenging activity, when liposomes were used as target systems, a fact which may be related to
Synthesis of diverse analogues of Oenostacin and their antibacterial activities
Srivastava, Vandana,Darokar, Mahendra P.,Fatima, Atiya,Kumar,Chowdhury, Chinmay,Saxena, Hari Om,Dwivedi, Gaurav R.,Shrivastava, Kunal,Gupta, Vivek,Chattopadhyay,Luqman, Suaib,Gupta,Negi, Arvind S.,Khanuja, Suman P.S.
, p. 518 - 525 (2008/03/12)
Several diverse analogues of Oenostacin, a naturally occurring potent antibacterial phenolic acid derivative, have been synthesized. A small library with more than forty analogues having different aromatic rings and varied side chains has been achieved through solution phase synthesis. Some of these analogues, that is, 22, 23 and 42, possessed potent antibacterial activities against Staphylococcus epidermidis and Staphylococcus aureus having EC50 ranging from 0.49 to 0.67 μM as compared to Oenostacin (EC50 = 0.12 μM).
Conformational analysis of a trihydroxylated derivative of cinnamic acid - A combined Raman spectroscopy and Ab initio study
Fiuza,Van Besien,Milhazes,Borges,Marques
, p. 103 - 118 (2007/10/03)
A conformational analysis of 3-(3,4,5-trihydroxyphenyl)-2-propenoic acid (3,4,5-trihydroxycinnamic acid, THPPE), a trihydroxylated cinnamic acid analogous to caffeic acid (a natural compound often present in diet), was carried out by Raman spectroscopy co
