78765-31-8Relevant articles and documents
Exploring cinnamic acid scaffold: development of promising neuroprotective lipophilic antioxidants
Chavarria, Daniel,Silva, Tiago,Martins, Daniel,Bravo, Joana,Summavielle, Teresa,Garrido, Jorge,Borges, Fernanda
, p. 1043 - 1053 (2015/06/25)
New lipophilic hydroxycinnamic acid based derivatives were designed and synthesized and their antioxidant and neuroprotective activities evaluated. The chemical modification introduced in the cinnamic acid scaffold leads to compounds with amplified lipophilicity and in general with increased antioxidant activity when compared to natural models (caffeic and ferulic acids). The compounds did not display cytotoxicity and present a significant neuroprotective effect against 6-OH-DA induced damage to SH-SY5Y cells. Compound 6 stands out as an efficient radical scavenger and iron(ii) chelator that ensures drug-like properties. Moreover, neuroprotection against oxidative damage was observed even at low concentration (1 μM). Therefore, compound 6 developed by a biology-oriented approach displays a combination of important features for a further optimization process that will generate a new effective antioxidant with therapeutic application for oxidative-stress-related events, namely neurodegenerative diseases.
The taming of capsaicin. Reversal of the vanilloid activity of N-acylvanillamines by aromatic iodination
Appendino, Giovanni,Daddario, Nives,Minassi, Alberto,Moriello, Aniello Schiano,De Petrocellis, Luciano,Di Marzo, Vincenzo
, p. 4663 - 4669 (2007/10/03)
Aromatic iodination ortho to the phenolic hydroxyl reverts the activity of the ultrapotent vanilloid agonist resiniferatoxin (RTX, 1a), generating the ultrapotent antagonist 5′-iodoRTX (1b). To better understand the role of iodine in this remarkable switch of activity, a systematic investigation on the halogenation of vanillamides, a class of compounds structurally simpler than resiniferonoids, was carried out. The results showed that (a) the antagonistic activity depends on the site of halogenation and is maximal at C-6′, (b) iodine is more efficient than chlorine and bromine at reverting the agonistic activity, and (c) iodine-carbon exchange decreases antagonist activity. Iodine-induced reversal of vanilloid activity was also observed in vanillamides more powerful than capsaicin, but a poor correlation was found between agonistic and antagonistic potencies, suggesting that differences exist in the way vanillamides and their 6′-iodo derivatives bind to TRPV1.″
(2E,4E)-N-(4-(1H-indol-3-yl)piperidin-1-yl)alkyl-5-(substituted phenyl)-2,4-pentadienamides as antiallergic agents with antihistaminic and anti slow-reacting substance (SRS) activities
Shigenaga,Manabe,Matsuda,Fujii,Matsuo
, p. 3 - 10 (2007/10/02)
As an extension of our study aiming to discover a novel compound with dual activities against histamine and slow-reacting substance (SRS), we synthesized two types of indolylpiperidine derivatives, 3 and 4-20. Testing for in vivo antianaphylactic activity and for in vitro anti-SRS activity revealed that (2E,4E)-5-(3,5-dimethoxy-4-hydroxyphenyl)-N-(2-(4-(1H-indol-3-yl)piper idin-1-yl)ethyl)-2,4-pentadienamide (11) exhibited potent dual activities with ED50 = 0.89 mg/kg and IC50 = 1.43 μM, respectively. However, the plasma concentration of unchanged 11 was very low when administered orally in guinea pigs. This result can be explained by fast formation of a glucuronic acid conjugate.
