Factors Influencing the Antifolate Activity of Synthetic Tea-Derived Catechins

Abstract

Novel tea catechin derivatives have been synthesized, and a structure-activity study, related to the capacity of these and other polyphenols to bind dihydrofolate reductase (DHFR), has been performed. The data showed an effective binding between all molecules and the free enzyme, and the dissociation constants of the synthetic compounds and of the natural analogues were on the same order. Polyphenols with a catechin configuration were better DHFR inhibitors than those with an epicatechin configuration. Antiproliferative activity was also studied in cultured tumour cells, and the data showed that the activity of the novel derivatives was higher in catechin isomers. Derivatives with a hydroxyl group para on the ester-bonded gallate moiety presented a high in vitro binding to DHFR, but exhibited transport problems in cell culture due to ionization at physiologic pHs. The impact of the binding of catechins to serum albumin on their biological activity was also evaluated. The information provided in this study could be important for the design of novel medicinal active compounds derived from tea catechins. The data suggest that changes in their structure to avoid serum albumin interactions and to facilitate plasmatic membrane transport are essential for the intracellular functions of catechins.

From tea to treatment; epigallocatechin gallate and its potential involvement in minimizing the metabolic changes in cancer

“…Catechins are hydroxy and gallate substitutions of the flavan-3-ol structure, each with relative bioactive effects [32]. Chemotherapeutically, the gallocylated catechins, GC, EGC, GCG, and EGCG are noted to possess the most chemotherapeutically active role [33][34][35][36][37].…”

Inhibitory and Activating Effects of Some Flavonoid Derivatives on Human Pyruvate Kinase Isoenzyme M2

“…They prevent against various pathological disorders and attention has been paid due to their pharmacological effects such as anticancer, anti‐oxidation, anti‐aging, antibacterial and antiviral activities, enzyme inhibition or activation . Several studies have reported that the potential effects of flavonoids on the enzyme inhibition or activation are related with their chemical structure like the number, positions, and types of substitutions . This study was aimed to investigate potential effects of some flavonoid derivatives with similar chemical structure on human PKM2.…”

Estudos químico e biológico de taninos e antraquinonas que atuam no sistema gastrointestinal

“…This is highlighted by some authors, as Ottaviani et al (2011), who report that (-)-epicatechin is the only stereoisomer capable of mediating a significant arterial dilation between some tested catechins. Other activities of these molecules when present in biological systems have been reported (DONOVAN et al, 2006;SAEZ-AYALA et al, 2013;SIRK et al, 2009;TAYLOR;HAMILTON-MILLER;STAPLETON, 2005).…”