Phenethyl ester and amide of Ferulic Acids: Synthesis and bioactivity against P388 Leukemia Murine Cells

Synthesis of a Cinnamic Acid Derivative and Bioactivity as an Anticancer Based on Result Quantitative Structure Activity Relationship (QSAR) Analysis

“…In the conversion of hydroxyl groups, caffeic acid into ester groups and the conversion of carboxylic acid groups to amides resulted in a decrease in polarity of the compound and its stability also increased, thus allowing the bioactivity of compounds to increase. This is reflected by the IC50 value of compound 3 against murine leukaemia P-388 cells of 0.5 µg / mL, while caffeic acid gives an IC50 of 54.31 µg / mL (Son, 2002) Comparing the results of previous studies on the bioactivity of amide analogue compounds against murine leukaemia P-388 cells, namely phenethyl trans-3-(4hydroxy-3-methoxyphenyl)acrylate with IC50 of 10.79 μg/mL and trans-3-(4-hydroxy-3-methoxyphenyl)-Nphenethylacrylamide with IC50 of 29.14 μg/mL (Firdaus et al, 2016), the activity of compound 3 is higher than the two compounds.…”

Tailored Functionalization of Natural Phenols to Improve Biological Activity

“…The feruloyl and phenethyl groups were combined to synthesize the ester phenethyl trans -3-(4-hydroxy-3-methoxyphenyl)acrylate and the amide trans -3-(4-hydroxy-3-methoxyphenyl)- N -phenethylacrylamide [ 317 ]. Phenethyl ester and amides were studied for bioactivity as anticancer agents, proving more effective than the parent compound [ 318 ].…”

Natural and Synthetic Derivatives of Hydroxycinnamic Acid Modulating the Pathological Transformation of Amyloidogenic Proteins

“…Some HCA derivatives also showed potent and selective MAO-B (phenethyl ( E )-3-(4-hydroxyphenyl)acrylate being the most potent one) or moderate BChE (e.g., 3,4-dihydroxyphenethyl ( E )-3-(4-hydroxyphenyl)acrylate) inhibitory activity [ 86 ]. The synthesis of phenethyl E -3-(4-hydroxy-3-methoxyphenyl)acrylate and E -3-(4-hydroxy-3-methoxyphenyl)- N -phenethylacrylamide from ferulic acid with phenethyl alcohol and phenethylamine, respectively, was performed via indirect reaction, including acetylation for hydroxyl group protection, acid chloride formation, esterification/amidation, and deacetylation as a deprotection reaction [ 87 ]. Both compounds showed anticancer activity against P388 murine leukemia cells.…”

“…Other coupling reagents, i.e., benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate(BOP), 1-(bis(dimethylamino)methylene)-1 H -[1,2,3]triazolo[4,5- b ]pyridine-1-ium 3-oxide hexafluorophosphate (HATU), and dicyclohexylcarbodiimide (DCC) have been used for the preparation of ferulic [ 88 ] and caffeic acid esters and amides [ 89 ]. The nucleophilic hydroxyl groups were often protected via acetylation by acetic anhydride in the presence of pyridine [ 87 , 90 , 91 ] or other bases [ 92 , 93 ]. Other methods for the preparation of HCA esters and amides have been used and were thoroughly reviewed by de Armas-Ricard and co-authors in 2019 [ 89 ].…”

“…As previously described, esters and amides of coumaric, ferulic and caffeic acid possess numerous biological activities, e.g., antioxidant [ 82 , 83 , 86 , 89 , 94 , 95 , 96 ], anticancer [ 78 , 87 , 92 ], antibacterial [ 82 , 97 , 98 , 99 ], antifungal [ 100 , 101 , 102 ], antiviral [ 82 , 90 , 103 ], anti-inflammatory [ 104 , 105 , 106 ], and many other activities [ 84 , 107 , 108 ]. The most commonly described health beneficial properties of HCAs and their derivatives is antioxidant activity due to the phenolic hydroxyl group(s) on the main aromatic ring, which possess(es) the ability to react with free radicals and reactive oxygen species forming a resonance-stabilized phenoxyl radical.…”