79419-46-8Relevant academic research and scientific papers
Biological evaluation of natural and synthesized homovanillic acid esters as inhibitors of intestinal fatty acid uptake in differentiated Caco-2 cells
Lieder, Barbara,Hans, Joachim,Hentschel, Fabia,Geissler, Katrin,Ley, Jakob
, (2019/10/14)
With raising prevalence of obesity, the regulation of human body fat is increasingly relevant. The modulation of fatty acid uptake by enterocytes represents a promising target for body weight maintenance. Recent results demonstrated that the trigeminal active compounds capsaicin, nonivamide, and trans-pellitorine dose-dependently reduce fatty acid uptake in differentiated Caco-2 cells as a model for the intestinal barrier. However, non-pungent alternatives have not been investigated and structural determinants for the modulation of intestinal fatty acid uptake have not been identified so far. Thus, based on the previous results, we synthesized 23 homovanillic acid esters in addition to the naturally occurring capsiate and screened them for their potential to reduce intestinal fatty acid uptake using the fluorescent fatty acid analog Bodipy-C12 in differentiated Caco-2 cells as an enterocyte model. Whereas pre-incubation with 100 μM capsiate did not change fatty acid uptake by Caco-2 enterocytes, a maximum inhibition of ?47% was reached using 100 μM 1-methylpentyl-2-(4-hydroxy-3-methoxy-phenyl)acetate. Structural analysis of the 24 structural analogues tested in the present study revealed that a branched fatty acid side chain, independent of the chain length, is one of the most important structural motifs associated with inhibition of fatty acid uptake in Caco-2 enterocytes. The results of the present study may serve as an important basis for designing potent dietary inhibitors of fatty acid uptake.
Ester Derivatives of 2,6-Bis(1-pyrrolidinylmethyl)-4-benzamidophenol as Short-Acting Antiarrhythmic Agents. 1
Stout, David M.,Black, Lawrence A.,Barcelon-Yang, Cynthia,Matier, W. L.,Brown, Barry S.,et al.
, p. 1910 - 1913 (2007/10/02)
In an effort to find a replacement for the iv antiarrhythmic drug lidocaine having reduced systemic and central nervous system effects, activity against supraventricular as well as ventricular arrhythmias, and a biological half-life of less than 15 min, derivatives of the orally active class Ic clinical agent 2,6-bis(1-pyrrolidinylmethyl)-4-benzamidophenol, 1 (ACC-9358), were synthesized and tested.Compounds with ester groups attached to the phenyl ring were either weakly active or toxic.Replacement of the formanilide function with alkyl esters afforded compounds with antiarrhythmic activity in the range of 1.When the ester carboxyl was separated from the bis(aminomethyl)phenol by methylene units, very short half-lives were observed in human blood.In general, these compounds also had low lipophilic character.
