Potent and Nontoxic Chemosensitizer of P-Glycoprotein-Mediated Multidrug Resistance in Cancer: Synthesis and Evaluation of Methylated Epigallocatechin, Gallocatechin, and Dihydromyricetin Derivatives

Iris L.K. Wong, Bao Chao Wang, Jian Yuan, Liang Xing Duan, Zhen Liu, Tao Liu, Xue Min Li, Xuesen Hu, Xiao Yu Zhang, Tao Jiang, Sheng Biao Wan, Ming Cheung Chow

Research output: Journal article publicationJournal articleAcademic researchpeer-review

38 Citations (Scopus)


We are interested in developing novel natural product-derived P-gp inhibitors to reverse cancer drug resistance. Here, we have synthesized 55 novel derivatives of methylated epigallocatechin (EGC), gallocatechin (GC), and dihydromyricetin (DHM). Three EGC derivatives (23, 35, and 36) and three GC derivatives (50, 51, and 53) are significantly better than epigallocatechin gallate (EGCG) with a relative fold (RF) ranging from 31.4 to 53.6. The effective concentration (EC50) of 23 and 51 ranges from 102 to 195 nM. Compounds 23 and 51 are noncytotoxic to fibroblasts with IC50 > 100 μM. Compound 23 is specific for P-gp without modulating activity toward MRP1 or BCRP. Compounds 23 and 51 are non-P-gp substrates. Important pharmacophores for P-gp modulation were identified. In summary, methylated EGC and GC derivatives represent a new class of potent, specific, noncytotoxic, and nonsubstrate P-gp modulators.
Original languageEnglish
Pages (from-to)4529-4549
Number of pages21
JournalJournal of Medicinal Chemistry
Issue number11
Publication statusPublished - 11 Jun 2015

ASJC Scopus subject areas

  • Molecular Medicine
  • Drug Discovery

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