96826-11-8Relevant articles and documents
A new multifunctional hydroxytyrosol-clofibrate with hypolipidemic, antioxidant, and hepatoprotective effects
Xie, Yun-Dong,Chen, Zi-Zhang,Shao, Li-Hua,Wang, Qiu-Tang,Li, Na,Lu, Wen-Fang,Xu, Yan-Hong,Gao, Yu-Qiong,Guo, Li-Ying,Liu, Hao-Le,Li, Yi-Ping,Yang, Guang-De,Bian, Xiao-Li
, p. 3119 - 3122 (2018)
Oxidative stress has been regarded as the leading mechanism of the hepatotoxicity of clofibrate (CF). To achieve multifunctional novel hypolipidemic agents with hypolipidemia, antioxidant, and ameliorating liver injury, clofibric acid derivative hydroxytyrosol-clofibrate (CF-HT) was synthesized by molecular hybridization. CF-HT exhibited significant hypolipidemia, reducing serum triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 30%, 33%, and 29% in hyperlipidemic mice induced by Triton WR 1339. CF-HT also shown hepatoprotective effect, a significant decrease in hepatic indices toxicity was observed, i.e. aspartate and lactate transaminases (AST and ALT) activities, alkalines phosphatases (ALP), and total bilirubin (TBIL) levels. The liver weight and liver coefficient were also ameliorated. Serum superoxide dismutase (SOD) was significantly elevated, and serum catalase (CAT) and malondialdehyde (MDA) content were remarkably restored. The hepatic glutathione (GSH) content was obviously increased and hepatic oxidized glutathione (GSSG) content was reduced dramatically by CF-HT, as compared to the CF treated mice (p 0.05). Moreover, the histopathological damage that hepatocyte hyperplasia and hypertrophy was also significantly ameliorated by treatment with CF-HT. Therefore, the results indicated that CF-HT exerted more potent hypolipidemic activity and definite hepatoprotective effect which may mainly be associated with its antioxidative property in mice.
Hydroxytyrosol nicotinate, a new multifunctional hypolipidemic and hypoglycemic agent
Xie, Yun-Dong,Chen, Zi-Zhang,Li, Na,Lu, Wen-Fang,Xu, Yan-Hong,Lin, Yuan-Yuan,Shao, Li-Hua,Wang, Qiu-Tang,Guo, Li-Ying,Gao, Yu-Qiong,Yang, Guang-De,Li, Yi-Ping,Bian, Xiao-Li
, p. 715 - 724 (2018)
Hydroxytyrosol (HT) is a natural polyphenol antioxidant that exists in olive oil. In the study of multifunctional hypolipidemic of nicotinic derivatives, we found that hydroxytyrosol nicotinate (HT-N) incorporation of niacin with HT displayed α-glucosidase inhibitory activities in vitro, such as yeast α-glucosidase (IC50 = 117.72 μM) and rat intestinal α-glucosidases maltase (IC50 = 31.86 μM) and sucrase (IC50 = 22.99 μM), and had a good control of postprandial blood glucose (PBG). HT-N shown significantly hypoglycemic action by 16.9% and protection of pancreatic tissue in type 2 diabetic mellitus (T2DM) mouse model. HT-N also shown a potent antioxidant activity and property of anti-glycation in vitro, which were benefit for ameliorating diabetic complications. Moreover, HT-N exhibited much significant hypolipidemia, lowering plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 34.6%, 45.8% and 32.1% respectively, in hyperlipidemic mice induced by Triton WR 1339. The results indicated that HT-N has hypolipidemic, hypoglycemic and antioxidant actions. All these properties could be conducive to amelioration of oxidative stress, hyperlipidemia, and diabetes that HT-N may serve as a multifunctional potential therapeutic strategy in diabetic patients with hyperlipidemia.
Straightforward access to novel mitochondriotropics derived from 2-arylethanol as potent and selective antiproliferative agents
Hicke, Francisco J.,Puerta, Adrián,Dini?, Jelena,Pe?i?, Milica,Padrón, José M.,López, óscar,Fernández-Bola?os, José G.
, (2021/12/01)
The necessity for developing novel cytostatic agents with improved activities and reduced side-effects to tackle cancer prompted us to investigate mitochondria-targeted compounds, an approach that is gaining attention for the selective transportation of cytotoxic agents. We envisioned the possibility of conjugating a phenethyl alcohol motif, decorated with a series of phenol-based substituents on the aryl moiety, with a triphenyl phosphonium scaffold (a mitochondria-directed vector), through a hydrocarbon chain of different lengths. Thus, such compounds that incorporate the phenethyl skeleton can be considered as masked phenolic compounds derived from relevant natural counterparts found in olive tree (e.g. tyrosol, hydroxytyrosol). Title compounds exhibited very strong in vitro antiproliferative activities against the panel of six human tumor cell lines tested, with GI50 values ranging from the nanomolar (0.026 ± 0.010 μM for 36) to the submicromolar range in most of the cases; this represents an improvement of up to 350-fold compared to classical chemotherapeutic agents, like 5-fluorouracil or cisplatin. Interestingly, decrease in the linker length led to an increase of GI50 values against non-tumor cells, thus allowing a remarkable improvement of selectivity (SI up to 269). The very promising antiproliferative activities prompted us to further investigate their behaviour against multidrug resistant cell lines (MDR). The results indicated a reduced sensitivity of the multidrug resistant cells to compounds, probably due to P-gp-mediated efflux of these antiproliferative agents. Interestingly, activities were completely restored to the same levels by co-administration of tariquidar, a well-known inhibitor of P-gp. Flow cytometry analysis on sensitive cell lines revealed a decrease in the percentage of cells in G1 phase accompanied by increase in S and G2/M phases. In addition, a significant increase in subG1 area, was observed. These results are compatible with the necrotic and apoptotic cell death detected in the Annexin V assay, and with the depolarization of the mitochondria membrane. Thus, the new mitochondriotropic agents reported herein can be considered as promising antiproliferative agents, endowed with remarkable potency and selectivity, including MDR cells, upon co-administration with a pump-efflux inhibitor.
2-(3,4-DIHYDROXYPHENYL)ETHYL 3-HYDROXYBUTANOATE, COMPOSITION, AND METHOD FOR IMPROVING FUNCTION OF AORTIC ENDOTHELIAL CELL
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Paragraph 0039; 0041, (2021/02/19)
The disclosure relates to a compound, 2-(3,4-dihydroxyphenyl)ethyl 3-hydroxybutanoate, for improving aortic endothelial cell function and use thereof. The compound is capable of inhibiting inflammatory response of the human aortic endothelial cells caused by a saturated fatty acid, and preventing an occurrence and progression of atherosclerosis. The compound is capable of reducing human aortic endothelial inflammation caused by a saturated fatty acid, for example, reducing the mRNA levels of interleukin-6 (IL-6), and is capable of effectively protecting the function of mitochondria in human aortic endothelium from being damaged by a saturated fatty acid, for example, increasing the expression of mitochondrial complex I.
3,4-DIHYDROXYPHENETHYL 3-HYDROXYBUTANOATE, PREPARATION AND USE THEREOF
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Paragraph 0102; 0107, (2021/03/19)
The present disclosure discloses a novel compound, 3,4-dihydroxyphenethyl 3-hydroxybutanoate, a method for preparing the same and use of the same, and in particular, a compound of formula I, use of the compound of formula I, optically pure isomers of the compound, a mixture of enantiomers in any ratio, or pharmaceutically acceptable salts thereof in preparing health food and drug for relieving brain fatigue, improving learning and memory abilities, and ameliorating mania mood related to brain fatigue.
Synthesis and antioxidant activity of conjugates of hydroxytyrosol and coumarin
Li, Wen-Bo,Qiao, Xue-Peng,Wang, Zi-Xiao,Wang, Shuai,Chen, Shi-Wu
, (2020/11/09)
Antioxidants have been the subject of intense research interest due to their numerous health benefits. In this work, a series of new conjugates of hydroxytyrosol and coumarin were synthesized and evaluated for their free radical scavenging, toxicity and antioxidant mechanism in vitro. The all target compounds 14a–t exhibited better radical scavenging activity than BHT, hydroxytyrosol, and coumarin in both DPPH radical and ABTS+ radical cation scavenging assays. The structure-activity relationships study indicated that the number and position of hydroxyl groups on the coumarin ring were vital to a good antioxidant capacity. Furthermore, the most promising compound 14q showed less toxicity in hemolysis assay and weaker antiproliferative effects than BHT against normal WI-38 and GES cells, and enhanced viability of H2O2-induced HepG2 cells. Additionally, 14q decreased the apoptotic percentage of HepG2 cells, reduced the ROS produce and LDH release, and improved GSH and SOD levels in H2O2-treated HepG2 cells. Lastly, 14q exhibited more stability than hydroxytyrosol in methanol solution. These results revealed that conjugations of hydroxytyrosol and coumarin show better antioxidant capacity, and are the efficacious approach to finding novel potential antioxidant.
Convergent Total Synthesis of Lamellarins and Their Congeners
Morikawa, Daiki,Morii, Kazuki,Yasuda, Yuto,Mori, Atsunori,Okano, Kentaro
, p. 8603 - 8617 (2020/07/16)
A convergent total synthesis of lamellarins S and Z is described. The synthesis features a halogen dance of an easily accessible α,β-dibromopyrrole promoted by an ester moiety. The resultant β,β′-dibromopyrrole undergoes a ligand-controlled Suzuki-Miyaura coupling to provide a range of diarylated pyrrole derivatives. The established synthetic method was also applicable to the synthesis of ningalin B and lukianols A and B.
Synthesis and SARs of dopamine derivatives as potential inhibitors of influenza virus PAN endonuclease
Liao, Yixian,Ye, Yilu,Li, Sumei,Zhuang, Yilian,Chen, Liye,Chen, Jianxin,Cui, Zining,Huo, Lijian,Liu, Shuwen,Song, Gaopeng
, (2020/01/21)
Currently, influenza PAN endonuclease has become an attractive target for development of new drugs to treat influenza infections. Herein we report the discovery of new PAN endonuclease inhibitors derived from a chelating agent dopamine moiety. A series of dopamine amide derivatives and their conformationally constrained 1,2,3,4-tetrahydroisoquinoline-6,7-diol-based analogs were elaborated and assayed against influenza virus A/WSN/33 (H1N1). Most compounds exhibited moderate to excellent antiviral activities, generating a preliminary SARs. Among them, compounds 14 and 19 showed stronger anti-IAV activity compared with the reference Peramivir. Moreover, 14 and 19 demonstrated a concentration-dependent inhibition of PAN endonuclease based on both FRET assay and SPR assay. Docking studies were also performed to elucidate the binding mode of 14 and 19 with the PAN protein and to identify amino acids involved in their mechanism of action, which were well consistent with the biological data. This finding was beneficial to laying the foundation for the rational development of more effective PAN endonuclease inhibitors.
A New Series of Salicylic Acid Derivatives as Non-saccharide α-Glucosidase Inhibitors and Antioxidants
Chen, Jiangang,Lu, Wenfang,Chen, Hao,Bian, Xiaoli,Yang, Guangde
, p. 231 - 246 (2019/02/19)
In this study, a series of salicylic acid derivatives were designed and synthesized as novel non-saccharide α-glucosidase inhibitors. Biological evaluation indicated that when compared to acarbose, compounds T9, T10, and T32 exhibited a higher potency of α-glucosidase inhibitory activity with IC50 values of 0.15±0.01, 0.086±0.01 and 0.32±0.02mM, respectively. Evaluation of the inhibition kinetics indicated that T9, T10, T32, and acarbose interacted with α-glucosidase in a mixed non-competitive inhibitory manner. Moreover, T9, T10, and T32 statically quenched the fluorescence of α-glucosidase by formation of an inhibitor-α-glucosidase complex. The docking results showed that hydrogen bonds were generated between the test compounds and α-glucosidase. The antioxidant study revealed that compound T10 exhibited a higher antioxidant activity via scavenging 1,1-diphenyl-2-picrylhydrazyl free radical (DPPH), thereby inhibiting lipid peroxidation and the total reduction capacity. In brief, the salicylic acid derivatives identified in this study were promising candidates for development as novel non-saccharide α-glucosidase inhibitors.
A new multifunctional hydroxytyrosol-fenofibrate with antidiabetic, antihyperlipidemic, antioxidant and antiinflammatory action
Xie, Yundong,Xu, Yanhong,Chen, Zizhang,Lu, Wenfang,Li, Na,Wang, Qiutang,Shao, Lihua,Li, Yiping,Yang, Guangde,Bian, Xiaoli
, p. 1749 - 1758 (2017/09/28)
Dyslipidemia, oxidative stress and inflammation are major risky factors involved in the pathophysiology of type 2 diabetes mellitus and atherosclerosis. Multifunctional intervene is more meaningful. The aim of this study was to evaluate the multifunctional effects of two new compounds, combination of fenofibric acid (FA) with tyrosol (T) or hydroxytyrosol (HT). Compared with fenofibrate (FF), FF-HT exhibited excellent antioxidant capacities in vitro and much improved hypolipidemia, reducing plasma triglyceride (TG), total cholesterol (TC), and malonaldehyde (MDA) by 76%, 54%, and 28%, while FF-T decreased the plasma parameters by 16%, 10%, and 20% in hyperlipidemic mice induced by Triton WR 1339. Furthermore, compound FF-HT exhibited significant antihyperglycemic, antihyperlipidemic, antioxidant and anti-inflammatory activities as well as attenuating hepatotoxicity in a type 2 diabetes experimental mouse model. The histological findings showed that FF-HT suppressed the development of hepatic lipid accumulation and ameliorated the damage in hepatic and pancreatic tissues compared to model mice. This study indicates for the first time that reasonable optimized drug design produce a compound entity which is conducive to the prevention of type 2 diabetes mellitus and its complications.
