Novel Perbutyrylated Glucose Derivatives of (–)-Epigallocatechin-3-Gallate Inhibit Cancer Cells Proliferation by Decreasing Phosphorylation of the EGFR: Synthesis, Cytotoxicity, and Molecular Docking

Abstract

Lung cancer is one of the most commonly occurring cancer mortality worldwide. The epidermal growth factor receptor (EGFR) plays an important role in cellular functions and has become the new promising target. Natural products and their derivatives with various structures, unique biological activities, and specific selectivity have served as lead compounds for EGFR. D-glucose and EGCG were used as starting materials. A series of glucoside derivatives of EGCG (7–12) were synthesized and evaluated for their in vitro anticancer activity against five human cancer cell lines, including HL-60, SMMC-7721, A-549, MCF-7, and SW480. In addition, we investigated the structure-activity relationship and physicochemical property–activity relationship of EGCG derivatives. Compounds 11 and 12 showed better growth inhibition than others in four cancer cell lines (HL-60, SMMC-7721, A-549, and MCF), with IC50 values in the range of 22.90–37.87 μM. Compounds 11 and 12 decreased phosphorylation of EGFR and downstream signaling protein, which also have more hydrophobic interactions than EGCG by docking study. The most active compounds 11 and 12, both having perbutyrylated glucose residue, we found that perbutyrylation of the glucose residue leads to increased cytotoxic activity and suggested that their potential as anticancer agents for further development.

Green Tea Polyphenol (-)-Epigallocatechin-3-Gallate (EGCG): A Time for a New Player in the Treatment of Respiratory Diseases?

“…Insertion of a specific chain of chemical groups into the molecule of EGCG should protect the reactive hydroxyl groups of EGCG and thereby increase the stability, improve the interaction of EGCG with lipid membranes, and to enhance cellular absorption [ 245 ]. Favorable results have been obtained from methyl-protected EGCG [ 246 ], EGCG monoester derivatives [ 247 , 248 ], alkyl-analogues [ 245 , 249 ], and glycoconjugates [ 250 , 251 ].…”

Preventive and therapeutic effects of green tea on lung cancer: a narrative review of evidence from clinical and basic research

“…Further studies with high level of evidence are needed to investigate the long-term efficacy and safety of oral administration of EGCG in lung cancer patients. In addition, some studies also revealed that the derivates of EGCG also exert anti-lung cancer activity ( 25 , 80 , 81 ). The anti-lung cancer activity of these derivates needs to be investigated by further studies.…”