132335-97-8Relevant articles and documents
Mild reaction of primary alcohols with ferulic acid
Bakholdina,Khlebnikov,Sevodin
, p. 441 - 443 (2016)
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Inhibition of mammalian carbonic anhydrase isoforms I-XIV with a series of phenolic acid esters
Maresca, Alfonso,Akyuz, Gulay,Osman, Sameh M.,Alothman, Zeid,Supuran, Claudiu T.
, p. 7181 - 7188 (2015)
A series of phenolic acid esters incorporating caffeic, ferulic, and p-coumaric acid, and benzyl, m/p-hydroxyphenethyl- as well as p-hydroxy-phenethoxy-phenethyl moieties were investigated for their inhibitory effects against the metalloenzyme carbonic anhydrase (CA, EC 4.2.1.1). Many of the mammalian isozymes of human (h) or murine (m) origin, hCA I-hCA XII, mCA XIII and hCA XIV, were inhibited in the submicromolar range by these derivatives (with KIs of 0.31-1.03 μM against hCA VA, VB, VI, VII, IX and XIV). The off-target, highly abundant isoforms hCA I and II, as well as hCA III, IV and XII were poorly inhibited by many of these esters, although the original phenolic acids were micromolar inhibitors. These phenols, like others investigated earlier, possess a CA inhibition mechanism distinct of the sulfonamides/sulfamates, clinically used drugs for the treatment of a multitude of pathologies, but with severe side effects due to hCA I/II inhibition. Unlike the sulfonamides, which bind to the catalytic zinc ion, phenols are anchored at the Zn(II)-coordinated water molecule, binding more externally within the active site cavity, and making contacts with amino acid residues at the entrance of the active site. As this is the region with the highest variability between the many CA isozymes found in mammals, this class of compounds shows isoform-selective inhibitory profiles, which may be exploited for obtaining pharmacological agents with less side effects compared to other classes of inhibitors.
Synthesis and activity towards Alzheimer's disease in vitro: Tacrine, phenolic acid and ligustrazine hybrids
Li, Guoliang,Hong, Ge,Li, Xinyu,Zhang, Yan,Xu, Zengping,Mao, Lina,Feng, Xizeng,Liu, Tianjun
, p. 238 - 254 (2018/02/20)
A series of novel tacrine-phenolic acid dihybrids and tacrine-phenolic acid-ligustrazine trihybrids were synthesized, characterized and screened as novel potential anti-Alzheimer drug candidates. These compounds showed potent inhibition activity towards cholinesterases (ChEs), among of them, 9i was the most potent one towards acetylcholinesterase (eeAChE, IC50 = 3.9 nM; hAChE, IC50 = 65.2 nM). 9i could also effectively block β-amyloid (Aβ) self-aggregation with an inhibition ratio of 47% at 20 μM. In addition, its strong anti-oxidation activity could protect PC12 cells from CoCl2-damage in the experimental condition while no neurotoxicity. Furthermore, its hepatotoxicity was lower than tacrine in vitro and in vivo. Kinetic and molecular modeling studies revealed that 9i worked in a mixed-type way, could interact simultaneously with catalytic active site (CAS) and peripheral anionic site (PAS) of AChE. Therefore, 9i was a promising multifunctional candidate for the treatment of AD.
