138769-50-3Relevant articles and documents
7-O-Esters of taxifolin with pronounced and overadditive effects in neuroprotection, anti-neuroinflammation, and amelioration of short-term memory impairment in vivo
Decker, Michael,Fischer, Wolfgang,Gunesch, Sandra,Hoffmann, Matthias,Kiermeier, Carolina,Maher, Pamela,Maurice, Tangui,Pinto, Antonio F. M.
, (2020)
Alzheimer's disease (AD) is a multifactorial disease and the most common form of dementia. There are no treatments to cure, prevent or slow down the progression of the disease. Natural products hold considerable interest for the development of preventive neuroprotectants to treat neurodegenerative disorders like AD, due to their low toxicity and general beneficial effects on human health with their anti-inflammatory and antioxidant features. In this work we describe regioselective synthesis of 7-O-ester hybrids of the flavonoid taxifolin with the phenolic acids cinnamic and ferulic acid, namely 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin. The compounds show pronounced overadditive neuroprotective effects against oxytosis, ferroptosis and ATP depletion in the murine hippocampal neuron HT22 cell model. Furthermore, 7-O-cinnamoyltaxifolin and 7-O-feruloyltaxifolin reduced LPS-induced neuroinflammation in BV-2 microglia cells as assessed by effects on the levels of NO, IL6 and TNFα. In all in vitro assays the 7-O-esters of taxifolin and ferulic or cinnamic acid showed strong overadditive activity, significantly exceeding the effects of the individual components and the equimolar mixtures thereof, which were almost inactive in all of the assays at the tested concentrations. In vivo studies confirmed this overadditive effect. Treatment of an AD mouse model based on the injection of oligomerized Aβ25-35 peptide into the brain to cause neurotoxicity and subsequently memory deficits with 7-O-cinnamoyltaxifolin or 7-O-feruloyltaxifolin resulted in improved performance in an assay for short-term memory as compared to vehicle and mice treated with the respective equimolar mixtures. These results highlight the benefits of natural product hybrids as a novel compound class with potential use for drug discovery in neurodegenerative diseases due to their pharmacological profile that is distinct from the individual natural components.
Synthetic Guaiacol Derivatives as Promising Myeloperoxidase Inhibitors Targeting Atherosclerotic Cardiovascular Disease
Premkumar, Jayaraj,Sampath, Parthasarathy,Sanjay, Rajagopalan,Chandrakala, Aluganti,Rajagopal, Desikan
supporting information, p. 1187 - 1199 (2020/05/25)
Myeloperoxidase (MPO) is known to cause oxidative stress and inflammation leading to cardiovascular disease (CVD) complications. MPO-mediated oxidation of lipoproteins leads to dysfunctional entities altering the landscape of lipoprotein functionality. The specificity of guaiacol derivatives toward preventing MPO-mediated oxidation to limit MPO's harmful effects is unknown. Diligent in silico studies were accomplished for a portfolio of compounds with guaiacol as a building block. The compounds’ activity toward MPO inhibition was also validated. The role of these chemical entities in controlling MPO-mediated oxidation of lipoproteins (LDL and HDL) was shown to agree with our approach of developing powerful MPO inhibitors. The mechanism of MPO inhibition was demonstrated to be reversible in nature. This study reveals that there is great potential for guaiacol derivatives as therapeutics for CVD by modulating lipid profiles, reducing atherosclerotic plaque burden, and subsequently optimizing cardiovascular functions.
L-type amino acid transporter 1 utilizing prodrugs of ferulic acid revealed structural features supporting the design of prodrugs for brain delivery
Puris, Elena,Gynther, Mikko,Huttunen, Johanna,Auriola, Seppo,Huttunen, Kristiina M.
, p. 99 - 109 (2019/01/11)
Ferulic acid (FA), a natural antioxidant, has displayed some potential benefits against Alzheimer's disease. However, due to its poor blood-brain barrier (BBB) permeation and low bioavailability, the clinical use of FA for the treatment of Alzheimer's dis
