102-37-4Relevant articles and documents
Discovery of neurotrophic agents based on hydroxycinnamic acid scaffold
Hosseini, Razieh,Moosavi, Fatemeh,Rajaian, Hamid,Silva, Tiago,Magalh?es e Silva, Diogo,Soares, Pedro,Saso, Luciano,Edraki, Najmeh,Miri, Ramin,Borges, Fernanda,Firuzi, Omidreza
, p. 926 - 937 (2016)
The number of people affected by neurodegenerative disorders such as Alzheimer's disease and Parkinson's disease is rapidly increasing owing to the global increase in life expectancy. Small molecules with neurotrophic effects have great potential for management of these neurological disorders. In this study, different (C1–C12) alkyl ester derivatives of hydroxycinnamic acids (HCAs) were synthesized (a total of 30 compounds). The neurotrophic capacity of the test compounds was examined by measuring promotion of survival in serum-deprived conditions and enhancement of nerve growth factor (NGF)-induced neurite outgrowth in PC12 neuronal cells. p-Coumaric, ferulic, and sinapic acids and their esters did not alter cell survival, while caffeic acid and all its alkyl esters, especially decyl and dodecyl caffeate, significantly promoted neuronal survival at 25?μm. Methyl, ethyl, propyl, and butyl caffeate esters also significantly enhanced NGF-induced neurite outgrowth, among which the most effective ones were propyl and butyl esters, which at 5?μm led to 25- and 22-fold increases in the number of neurites, respectively. The findings of the docking study suggested phosphatidylinositol 3-kinase (PI3K) as the potential molecular target. In conclusion, our findings demonstrate that alkyl esters of caffeic acid can be useful as scaffolds for the discovery of therapeutic agents for neurodegenerative diseases.
Design and synthesis of novel aspirin-caffeic acid ester hybrids for cardioprotection with reduced risk of hemorrhagic stroke
Shi, Zhi-Hao,Li, Nian-Guang,Tang, Yu-Ping,Shi, Qian-Ping,Zhang, Wei,Zhang, Peng-Xuan,Dong, Ze-Xi,Li, Wei,Duan, Jin-Ao
, p. 1342 - 1346 (2015)
A series of novel aspirin-caffeic acid ester hybrids for cardioprotection with reduced risk of hemorrhagic stroke were designed and synthesized by coupling aspirin and caffeic acid esters inspired by NCX-4016. The synthesized compounds were evaluated for
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Helferich,Vorsatz
, p. 191,192 (1935)
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Study on the formation of antihypertensive twin drugs by caffeic acid and ferulic acid with telmisartan
Li, Pengshou,Li, Ziyong,Ma, Qixiang,Peng, Yingying,Zhang, Xiaohua
, p. 977 - 992 (2020)
Purpose: This study aimed to synthesize twin drugs from cinnamic acid compounds, caffeic acid (CFA) and ferulic acid (FLA), which can antagonize endothelin-1 (ET-1) with telmisartan through ester bonds. Moreover, the antihypertensive effect of telmisartan and its influence on blood pressure variability (BPV) were enhanced, and the bioavailability of caffeic acid and ferulic acid was improved. Methods: Six twin drugs, which were the target compounds, were synthesized. Hypertensive rats (SHR) and conscious sinoaortic-denervated (SAD) rats were spontaneously used as models for pharmacodynamic research to study the antihypertensive efficacy of these twin drugs. Wistar rats were employed as pharmacokinetic research models to investigate the pharmacokinetics of the target compounds via intragastric administration. Cellular pharmacodynamic research was also conducted on the antagonistic action on Ang II-AT1, ETA and ETB receptor. Results: Compound 1a was determined as the best antihypertensive twin drug and thus was further studied for its effect on BPV. Compared with that of telmisartan, the antihypertensive effect of compound 1a was improved (p50 of Lps-2 was still two orders of magnitude higher than that of the positive drug telmisartan. Hence, the twin drugs worked by metabolizing and regenerating telmisartan and caffeic acid or ferulic acid in the body. Conclusion: The synthesized twin drugs improved telmisartan’s antihypertensive effects, significantly decreased BPV in SAD rats and increased the bioavailability of caffeic acid and ferulic acid. This study serves as a basis for the development of new angiotensin receptor blocker (ARB) in the future and a reference for the development of new drugs to antagonize ET-1.
Structure-based design and synthesis of new 4-methylcoumarin-based lignans as pro-inflammatory cytokines (TNF-α, IL-6 and IL-1β)inhibitors
Santhosh Kumar,Sajeli Begum, Ahil,Hira, Kirti,Niazi, Sarfaraj,Prashantha Kumar,Araya, Hiroshi,Fujimoto, Yoshinori
, (2019)
Suppression of pro-inflammatory cytokines (TNF-α, IL-1β and IL-6)along with nitric oxide reduction in RAW 264.7 cells by 7,8-dihydroxy-4-methylcoumarin, ethyl p-coumarate, ethyl caffeate and ethyl ferulate drove us to search structural-analogues of the aforementioned compounds through structure-based drug design. Docking studies revealed that substituted cinnamic acids and their ethyl esters (2-7c)showed higher GoldScore-fitness (GSF)and non-bonding interactions with target proteins than 7,8-dihydroxy-4-methylcoumarin (1a)and 7,8-dihydroxy-5-methylcoumarin (1b). With this background, the methylcoumarins (1a and 1b)and the cinnamic acid derivatives (2-7c)were fused in different permutations and combinations to generate sixty novel fused-cyclic coumarinolignans (FCLs)(8–13k). Docking studies on 8–13k indicated that several FCLs possess higher GSF, interesting active site interactions and distinctive π-π interactions compared to the standards (cleomiscosin A, diclofenac Na and prednisolone). Based on these findings, four novel FCLs (9d, 10d, 11d and 11e)were synthesized and tested for inhibition effect on TNF-α, IL-1β and IL-6 expressions in LPS and oxalate crystal-induced in-vitro models. Compound 10d exhibited significant effect (P 50 value of 8.5 μM against TNF-α. Compound 11e possessed IC50 values of 13.29 μM and 17.94 μM against IL-6 and IL-1β, respectively. Study on SAR corroborated the requirement of C-4-methyl substituent in the coumarin moiety, dihydroxyl groups in the phenyl ring, and esterification of lignans for potent activity. Additionally, the reported excellent anti-inflammatory activity of cleomiscosin-A-glucoside was corroborated by from the higher GSF and better hydrophobic interactions than cleomsicosin A in the docking study. As an outcome, some novel and potentially active FCLs acting through NFκB and caspase 1 signaling pathways have been discovered as multiple cytokine inhibitors.
Orosensory-directed identification of astringent mouthfeel and bitter-tasting compounds in red wine
Hufnagel, Jan Carlos,Hofmann, Thomas
, p. 1376 - 1386 (2008)
Application of sequential solvent extraction, followed by HPLC combined with the taste dilution analysis, enabled the localization of the most intense velvety astringent, drying, and puckering astringent, as well as bitter-tasting, compounds in red wine,
Alkyl esters of hydroxycinnamic acids with improved antioxidant activity and lipophilicity protect PC12 cells against oxidative stress
Garrido, Jorge,Gaspar, Alexandra,Garrido, E. Manuela,Miri, Ramin,Tavakkoli, Marjan,Pourali, Samaneh,Saso, Luciano,Borges, Fernanda,Firuzi, Omidreza
, p. 961 - 967 (2012)
Hydroxycinnamic acids (HCAs) are phenolic compounds present in dietary plants, which possess considerable antioxidant activity. In order to increase the lipophilicity of HCAs, with the aim of improving their cellular absorption and expansion of their use in lipophilic media, methyl, ethyl, propyl and butyl esters of caffeic acid and ferulic acid have been synthesized. All caffeate esters had a slightly lower DPPH IC50 (13.5-14.5 μM) and higher ferric reducing antioxidant power (FRAP) values (1490-1588 mM quercetin/mole [mMQ/mole]) compared to caffeic acid (16.6 μM and 1398 mMQ/mole, respectively) in antioxidant assays. In contrast, ferulate esters were less active in DPPH (56.3-74.7 μM) and FRAP assays (193-262 mMQ/mole) compared to ferulic acid (44.6 μM and 324 mMQ/mole, respectively). Redox properties of HCAs were in line with their antioxidant capacities, so that compounds with higher antioxidant activities had lower oxidation potentials. Measurement of partition coefficients disclosed the higher lipophilicity of the esters compared to parent compounds. All esters of caffeic acid significantly inhibited hydrogen peroxide-induced neuronal PC12 cell death assessed by MTT assay at 5 and 25 μM. However, caffeic acid, ferulic acid and ferulate esters were not able to protect the cells. In conclusion, these findings suggest that alkyl esterification of some HCAs augments their antioxidant properties as well as their lipophilicity and as a consequence, improves their cell protective activity against oxidative stress. These compounds could have useful applications in conditions where oxidative stress plays a pathogenic role.
Enzymatic Synthesis and Antioxidant Activity of 1-Caffeoylglycerol Prepared from Alkyl Caffeates and Glycerol
Meng, Xiang-Yun,Xu, Yan,Wu, Jin-Xian,Zhu, Chang-Tong,Zhang, Dong-Yang,Wu, Guo-Hua,Wu, Fu-An,Wang, Jun
, p. 149 - 159 (2018)
Caffeic acid (CA) as a strong antioxidant has lower solubility in nonpolar media, which limits its application in the food industry. To increase the lipophilicity of CA, 1-caffeoylglycerol (1-CG) was synthesized by lipase-catalyzed transesterification of
Anchimerically Assisted Selective Cleavage of Acid-Labile Aryl Alkyl Ethers by Aluminum Triiodide and N, N-Dimethylformamide Dimethyl Acetal
Sang, Dayong,Yue, Huaxin,Zhao, Zhengdong,Yang, Pengtao,Tian, Juan
, p. 6429 - 6440 (2020/07/14)
Aluminum triiodide is harnessed by N,N-dimethylformamide dimethyl acetal (DMF-DMA) for the selective cleavage of ethers via neighboring group participation. Various acid-labile functional groups, including carboxylate, allyl, tert-butyldimethylsilyl (TBS), and tert-butoxycarbonyl (Boc), suffer the conditions intact. The method offers an efficient approach to cleaving catechol monoalkyl ethers and to uncovering phenols from acetal-type protecting groups such as methoxymethyl (MOM), methoxyethoxymethyl (MEM), and tetrahydropyranyl (THP) chemoselectively.
Structure?Activity Relationships of Cinnamate Ester Analogues as Potent Antiprotozoal Agents
Bernal, Freddy A.,Kaiser, Marcel,Wünsch, Bernhard,Schmidt, Thomas J.
, p. 68 - 78 (2019/11/22)
Protozoal infections are still a global health problem, threatening the lives of millions of people around the world, mainly in impoverished tropical and sub-tropical regions. Thus, in view of the lack of efficient therapies and increasing resistances against existing drugs, this study describes the antiprotozoal potential of synthetic cinnamate ester analogues and their structure-activity relationships. In general, Leishmania donovani and Trypanosoma brucei were quite susceptible to the compounds in a structure-dependent manner. Detailed analysis revealed a key role of the substitution pattern on the aromatic ring and a marked effect of the side chain on the activity against these two parasites. The high antileishmanial potency and remarkable selectivity of the nitro-aromatic derivatives suggested them as promising candidates for further studies. On the other hand, the high in vitro potency of catechol-type compounds against T. brucei could not be extrapolated to an in vivo mouse model.
