Structure-based design and synthesis of a novel long-chain 4''-alkyl ether derivative of EGCG as potent EGFR inhibitor: in vitro and in silico studies.

ABSTRACT: Herein, we report the discovery of a novel long-chain ether derivative of (-)-epigallocatechin-3-gallate (EGCG), a major green tea polyphenol as a potent EGFR inhibitor. A series of 4''-alkyl EGCG derivatives have been synthesized via regio-selectively alkylating the 4'' hydroxyl group in the D-ring of EGCG and tested for their antiproliferative activities against high (A431), moderate (HeLa), and low (MCF-7) EGFR-expressing cancer cell lines. The most potent compound, 4''-C₁₄ EGCG showed the lowest IC₅₀ values across all the tested cell lines. 4''-C₁₄ EGCG was also found to be significantly more stable than EGCG under physiological conditions (PBS at pH 7.4). Further western blot analysis and imaging data revealed that 4''-C₁₄ EGCG induce

SUBMITTER: Singh S 

PROVIDER: S-EPMC9201511 | biostudies-literature | 2022 Jun

REPOSITORIES: biostudies-literature