Investigation of the structure-activity relationship (SAR) of natural products ((-)-EGCG from green tea and YCK from Murraya Paniculata)

Abstract

In view of the attention on the biological activity of (-)-epigallocatechin gallate (EGCG) from green tea and YCK from Murraya Paniculata, this research aimed to study the structure-activity relationship (SAR) of these compounds. To this purpose, we have synthesized a series of EGCG, GCG (gallocatechin gallate) and YCK analogues. EGCG is very unstable in neutral or slightly alkaline medium and thus gives low bioavailability. We have prepared the protected EGCG as the peracetate esters. The experimental results indicate that protection of the hydroxyl groups not only increases the stability of the compound, but also elevates the drug potency. The synthetic EGCG peracetate can therefore serve as a prodrug. A series of racemic GCG analogues with modifications in the A or the G ring, and their peracetate esters, have been synthesized. From the SAR study of these analogues, it is concluded that both the hydroxyl groups on the A ring are important for the expression of antitumor activity. In addition hydroxyl group in either C-3" or C-4" on the G ring is essential for the antitumor effect. Among those synthetic GCG analogues, three of them show much higher drug potency than (-)-EGCG. For the SAR study of YCK, three known YCK analogues have been synthesized and their antitumor activities have been investigated. Although all the YCK analogues did not show stronger efficacy than their mother compound, an important structural feature has been found which can lay the groundwork for further YCK modification.